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Indications

Expanding the scope of use of vaccine for immunization against COVID-19 for ages 6 and older without dose adjustment.

Dose

2 Doses

Interval

21 – 28 days

Contraindication

• People with history of severe allergic reaction to CoronaVac and Covilo or other inactivated vaccine, or any component of CoronaVac and Covilo (active or inactive ingredients, or any material used in the process)
  
• Previous severe allergic reactions to any other vaccines(e.g., acute anaphylaxis, angioedema, dyspnea, etc.)

Caution

1. Hypersensitivity and anaphylaxis – Close observation for at least 30 minutes is recommended following vaccination
2. Common side effects: pain at injection site headache fever, fatigue, difficult breathing
3. Severe adverses events: nausea severe vomiting

1. To assign an easy-to-pronounce and non-stigmatizing name to emerging SARS-CoV-2 variants for monitoring and convenient public discussions.
2. To assess the impact of the evolution of SARS-CoV-2 related to disease severity, or the performance of vaccines, therapeutic medicines, diagnostic tools, or other public health and social measures.

1. Monitor changes to the virus so that if significant amino acid substitutions are identified
   
2. Inform countries and the public about any changes that may be needed to respond to the variant
   
3. Establish proven disease control methods/measures

1.  Variants of concern (VOC)
   • Meets VOI criteria and one or more below
     • Increase in transmissibility
     • Increase in virulence
     • Decrease in effectiveness of public health or available diagnostics, vaccines, therapeutics
   • Currently designated variants of concern; Alpha (B.1.1.7 ), Beta (B.1.351), Gamma (P.1), Delta (B.1.617.2) and Omicron (B.1.1.529).
2. Variants of interest (VOI)
   • Genetic changes that are predicted or known to affect virus characteristics such as transmissibility, disease severity, immune escape, diagnostic or therapeutic escape; AND
   • Identified to cause significant community transmission or multiple COVID-19 clusters, in multiple countries with increasing relative prevalence alongside increasing number of cases over time, or other apparent epidemiological impacts to suggest an emerging risk to global public health.
   • Currently designated variants of interest; Lambda (C.37) and Mu (B.1.621).
3. Variants under monitoring (VUM)
   • Variant with genetic changes that are suspected to affect virus characteristics, it may pose a future risk, but evidence of phenotypic or epidemiological impact is currently unclear, requiring enhanced monitoring and repeat assessment pending new evidence.
4. Formerly monitored variants
   • Former VOCs/VOIs/VUMs, including their descendent lineages, reclassified one or more below
     • The variant is no longer circulating at levels of global public health.
     • The variant has been circulating for a long time without any impact on the overall epidemiological situation.
     • The evidence demonstrates that the variant is not associated with any concerning properties

Still active to conduct comparative assessment of variant characteristics and public health risks and monitor and track global spread

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Indications

For active immunisation to prevent COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older as a primary series of two doses or a single booster dose at least five months after completing a primary series of the vaccine.

Dose

• 2 for primary series
  
• 1 for booster dose

Interval

• 28 days apart for primary series
  
•  at least 5 months for booster dose

Contraindication

Do not use COVID-19 Vaccine Moderna in individuals with hypersensitivity to the active substance or to any of the excipients

Caution

1. Hypersensitivity and anaphylaxis
2. Anxiety-related reactions
3. Concurrent illness
4. Thrombocytopenia and coagulation disorders
5. Immunocompromised individuals

Remark

It is also authorized for use as a heterologous (or “mix and match”) single booster dose for individuals 18 years of age and older following completion of primary vaccination with a different available COVID-19 vaccine

To examine the reactogenicity and immunogenicity, particularly omicron variant, of four heterologous boosters given at 6-month interval.

• A prospective cohort study
  
• Thai adults aged 18–70 years old 224 individuals who completed the two-dose CoronaVac for six months were included
  
• Participants were separated into four groups by conveniently sampling of 50–60 participants to receive one dose of Sinopharm, AstraZeneca, Pfizer and Moderna
  
• Blood samples were collected to measure the immune response for total Ig and IgG against receptor binding domain, and IgG against nucleocapsid (N)
  
• Measure neutralizing antibody by surrogate virus neutralization test Kit to wild-type, alpha, beta, delta, and omicron
  
• Focus reduction neutralization test
  
• Measured T cell response by Interferon-gamma release assay
  
• Statistical analysis

• RBD immunoglobulin (Ig), anti-RBD IgG, focus reduction neutralization test (FRNT50) against delta and omicron variants, and T cell response were highest in Moderna group followed by the Pfizer, Astrazeneca and Sinopharm groups, respectively.
• Witnessed a higher total Ig anti-RBD in the long-interval than in the short-interval groups.

• All four booster vaccines significantly increased binding and NAbs in individuals immunized with two doses of CoronaVac. The present evidence may benefit vaccine strategies development to thwart variants of concern, including the omicron variant
  
• Total Ig anti-RBD (U/mL) and IgG responses was higher in individuals receiving the viral vector and mRNA vaccines

To characterize the increase in immune response and neutralizing antibody induced by heterologous vaccination with AZD1222 (AstraZeneca) in Thai healthcare workers who were previously fully vaccinated with CoronaVac (Sinovac).

• Sera from 210 healthcare workers who received two doses of CoronaVac, followed by AstraZeneca in June-July 2021 were tested for anti-RBD IgG, anti-N IgG and anti- S1 IgA
  
• The neutralizing activities in a subset of serum samples were tested against the wild type and variants of concern Alpha Beta and Delta using an ELISA
  

Participants who received the booster of AstraZeneca possessed higher levels of spike RBD-specific IgG, total immunoglobulins, and anti-S1 IgA than the two-dose vaccinees (p < 0.001) and the neutralizing activity against the wild type and all variants of concern was higher than the recipients of the two-dose vaccines.

A three-dose heterologous regimen, two initial CoronaVac followed with a third AstraZeneca vaccine, induced a strong immunological response.

To compare the safety and immunogenicity of a third heterologous booster dose of one of three different vaccines, with a homologous boost in adults in Brazil who previously received two doses of CoronaVac

1. Adults (18 years and older) who had received two doses of CoronaVac 6 months previously were randomly assigned (5:6:5:5) stratified by site, age group (18–60 years or 61 years and over), and day of randomisation.
2. The third heterologous dose was of either Ad26.COV2-S, Janssen, BNT162b2, Pfizer–BioNTech, or AZD1222, AstraZeneca, compared with a third homologous dose of CoronaVac.
3. The primary outcome was non-inferiority of anti-spike IgG antibodies 28 days after the booster dose in the heterologous boost groups compared with homologous regimen
4. Secondary outcomes included neutralising antibody titres at day 28, local and systemic reactogenicity profiles, adverse events, and serious adverse events.

1. From baseline to day 28 after the booster vaccine, all groups had a substantial rise in IgG antibody concentrations: the geometric fold-rise was
   • 77% (95% CI 67–88) for Ad26.COV2-S
   • 152% (134–173) for BNT162b2
   • 90% (77–104) for ChAdOx1 nCoV-19
   • 12% (11–14) for CoronaVac
2. 2. Geometric mean ratios (heterologous vs homologous) were
   • 6.7 (95% CI 5.8–7.7) for Ad26.COV2-S
   • 13.4 (11.6–15.3) for BNT162b2
   • 7.0 (6.1–8.1) for ChAdOx1 nCoV-19
3. At day 28, all groups except for the homologous boost in the older adults reached 100% seropositivity: geometric mean ratios (heterologous vs homologous) were
   • 8.7 (95% CI 5.9–12.9) for Ad26.COV2-S
   • 21.5 (14.5–31.9) for BNT162b2
   • 10.6 (7.2–15.6) for ChAdOx1 nCoV-19
4. Live virus neutralising antibodies were also boosted against delta (B.1.617.2) and omicron variants (B.1.1.529).
5. Five serious adverse events. Three of which were considered possibly related to the vaccine received: one in the BNT162b2 group and two in the Ad26.COV2-S group. All participants recovered and were discharged home.

1. Antibody concentrations were low at 6 months after previous immunisation with two doses of CoronaVac.
2. All four vaccines administered as a third dose induced a significant increase in binding and neutralising antibodies, which could improve protection against infection.
3. Heterologous boosting resulted in more robust immune responses than homologous boosting and might enhance protection.

To evaluate the effects of a heterologous BNT162b2 mRNA vaccine booster on the humoral immunity of participants that had received a two-dose regimen of CoronaVac

1. Plasma samples from 101 non-hospitalized adult participants who received the BNT162b2 booster dose at least four weeks after the second dose of CoronaVac vaccine between July 30 and August 27, 2021 were analyzed.
2. The mean ages of the participants (majority 78 females, 70%) was 40.4 ± 13.4
3. Data from a previous cohort, that received two doses of mRNA COVID-19 vaccines (Moderna or Pfizer) were used as reference.
4. Plasma antibody reactivity to Spike protein and receptor binding domain (RBD) of SARS-CoV-2 were measured at baseline, 7 and 28 days post BNT162b2 booster.

1. Heterologous CoronaVac prime followed by BNT162b2 booster regimen induces elevated virus-specific antibody levels and potent neutralization activity against the ancestral virus and Delta variant, resembling the titers obtained after two doses of mRNA vaccines.
2. Neutralization of Omicron was undetectable in participants that had received a two-dose regimen of CoronaVac vaccine
3. BNT162b2 booster resulted in a 1.4-fold increase in neutralization activity against Omicron, compared to two-dose mRNA vaccine.
4. Neutralizing antibody titers were reduced by 7.1-fold and 3.6-fold for Omicron compared to ancestral and Delta variants, respectively.

These findings have immediate implications for multiple countries that previously used a two-dose regimen of CoronaVac and are of particular importance considering the increasing global need for heterologous vaccine boosters as a relevant future strategy to combat the impact of emerging variants in countries where inactivated vaccines have been the dominant product used.

To compare PRNT₅₀ and PRNT₉₀ geometric mean antibody titres (GMTs) to wild-type SARS-CoV-2 and Omicron variants

1. Evaluated sera from
   1.  Vaccinated individuals with no evidence of prior COVID-19 infection
      • 3-5 weeks after receiving two doses of BNT162b2 or two doses of CoronaVac (randomly selected from a previous study)
      • 3-5 weeks after receiving a 3rd dose of CoronaVac or a heterologous booster dose of BNT162b2 after two prior doses of CoronaVac (randomly selected from a previous study)
      • receiving 3rd dose of BNT162b2
   2. Previously infected individuals:
      • who had recovered from COVID-19 (pre-omicron emergence) and had not yet received vaccine
      • who had received one dose of BNT162b2
      • who had received one dose of CoronaVac
2. PRNT₅₀ antibody titre ≥ 25.6 in our live virus assay corresponded to the threshold of 50% protection against WT SARS-CoV-2.

1.  Vaccinated individuals with no evidence of prior COVID-19 infection:
   1. 3-5 weeks after receiving two doses of BNT162b2
      • Wild-type virus GMT: 218.8
      • Omicron GMT: 7.0 (31.3 folds reduction)
      • Number of participants with PRNT₅₀ ≥ 25.6 (Omicron): 2/31
   2. 3-5 weeks after receiving two doses of CoronaVac
      • Wild-type virus GMT: 32.5
      • Omicron GMT: 5.0 (6.5 folds reduction)
      • Number of participants with PRNT₅₀ ≥ 25.6 (Omicron): 0/30
   3. 3-5 weeks after receiving a 3rd dose of CoronaVac
      • Wild-type virus GMT: 65
      • Omicron GMT: 8.9 (7.3 folds reduction)
      • Number of participants with PRNT₅₀ ≥ 25.6 (Omicron): 1/30
   4. 3-5 weeks after receiving heterologous booster dose of BNT162b2 after two prior doses of CoronaVac
      • Wild-type virus GMT: 305.5
      • Omicron GMT: 59.2 (5.2 folds reduction)
      • Number of participants with PRNT₅₀ ≥ 25.6 (Omicron): 24/30
   5. receiving 3rd dose of BNT162b2
      • Wild-type virus GMT: 320
      • Omicron GMT: 77.8 (4.1 folds reduction)
      • Number of participants with PRNT₅₀ ≥ 25.6 (Omicron): 22/25
2. Previously infected individuals:
   1. who had recovered from COVID-19 (pre-omicron emergence) and had not yet received vaccine
      • Wild-type virus GMT: 85.7
      • Omicron GMT: 8.1 (10.6 folds reduction)
      • Number of participants with PRNT₅₀ ≥ 25.6 (Omicron): 1/30
   2. who had received one dose of BNT162b2
      • Wild-type virus GMT: 320
      • Omicron GMT: 130 (2.5 folds reduction)
      • Number of participants with PRNT₅₀ ≥ 25.6 (Omicron): 29/30
   3. who had received one dose of CoronaVac
      • Wild-type virus GMT: 237.8
      • Omicron GMT: 29.7 (8.0 folds reduction)
      • Number of participants with PRNT₅₀ ≥ 25.6 (Omicron): 18/28

1. Limitation
   • Relativetly small numbers in the individual groups
   • Have not investigated other antibody activities and T cell response
2. Conclusion
   • Two doses of BNT162b2 or CoronaVac vaccines elicit low neutralizing antibodies against the Omicron variant.
   • Homologous or heterologous BNT162b2 booster doses following two doses of either BNT162b2 or CoronaVac improve neutralizing antibody levels against Omicron variant.
   • Three doses of CoronaVac failed to elicit neutralizing antibody responses to Omicron in most recipients.
   • Countries that primarily use CoronaVac vaccines may need to consider mRNA vaccine boosters in response to the spread of Omicron.

To determine antibody levels and cross-neutralization in patients with SARS-CoV-2 breakthrough infection following two doses of CoronaVac compared with those in uninfected individuals who received two doses of CoronaVac and those who received AZD1222 as third vaccination

1. Evaluated sera from
   • patients who had been completely vaccinated with two doses of CoronaVac then subsequently became infected with SARS-CoV-2 (The SARS-CoV-2 variants circulating in Thailand during the study period were alpha and delta)
   • unexposed SARS-CoV-2 individuals who had been fully vaccinated with two doses of CoronaVac (control) 1.3 fully vaccinated CoronaVac individuals who received AZD1222 as a third vaccination
2. All sera were tested for
   • SARS-CoV-2-specific binding antibody responses
   • Neutralizing activity against wild-type SARS-CoV-2 and variants including alpha, beta, and delta
   • Neutralizing antibody titres against delta and omicron

1. Total RBD-specific Ig was significantly increased in patients with breakthrough infection (18154 units per millilitre (U/mL); 95% CI 13506–24402 U/mL) compared to fully vaccinated individuals without infection (98 U/mL; 95% CI 83–116 U/mL) and those who received AZD1222 as a third vaccination (7947 U/mL; 95% CI 7277–8679).
2. Neutralizing activity in breakthrough infection patients
   • were significantly higher than those in unexposed individuals following complete CoronaVac vaccination (p < 0.001).
   • Compared to individuals who received AZD1222 as a third vaccination, in patients with breakthrough infection neutralizing activity was significantly higher for alpha (p = 0.02) and beta (p < 0.01) variants, but not wild-type or delta variants.
3. Neutralizing antibody titres in sera from patients with breakthrough infection
   • The geometric mean titres against delta were 1332 (95% CI 875–106 2026).
   • The geometric mean titres against omicron were 212 (95% CI 142–316) (6.3-fold reduction compared to delta (p < 0.001)).

Conclusion

1. Patients with breakthrough infection exhibited potent antibody responses, exceeding those of individuals who received AZD1222 as a third vaccination.
2. Breakthrough infection increased neutralizing activity that cross-inhibited SARS-CoV-2 variants corresponding to wild-type, alpha, beta, and delta.
3. Sera from patients with breakthrough infection exhibited less neutralizing activity against omicron than against delta.

Limitation

1. Small sample size
2. The SARS-CoV-2 variants that caused breakthrough infections were not identified.
3. Omicron neutralization assays were not conducted using sera from unexposed individuals who had been fully vaccinated with two doses of CoronaVac or those who received AZD1222 as a third vaccination.

To evaluate whether BNT162b2-elicited antibodies are capable of neutralizing the Omicron variant

• Pfizer immune sera from vaccinated individuals between 20-72 years of age were obtained from different clinical trials
  
  • at 21 days after two doses of Pfizer (32 participants)
    
  • at 1 month after the third dose of Pfizer (30 participants)
    
• Used pseudovirus and lived SARS-CoV-2 neutralization test
  

Figure 1 The level of GMT 21 days after receiving 2 doses and 1 month after receiving 3 doses of  Pfizer at Omicron by using Lived SARS-CoV-2 neutralization test compared to Wuhan

Figure 2 The level of GMT 21 days after receiving 2 doses and 1 month after receiving 3 doses of  Pfizer at Omicron by using  Pseudovirus neutralization test compared to Wuhan

• Lived neutralization test
  • GMT 21 days after receiving 2 doses of Pfizer at Omicron (6:368) compared to Wuhan.
  • GMT 1 month after receiving 3 doses of  Pfizer at Omicron is 106:6 and is still lower compared to 3 doses against Wuhan (106:368).
• Pseudovirus neutralization test
  • GMT 21 days after receiving 2 doses, 1 month after receiving 3 doses of Pfizer at Omicron are similar to the Lived neutralization test result.

         * GMT is the level of VNT that can neutralize lived virus and pseudovirus at 50%.

Two doses of  Pfizer may not be sufficient to protect against infection with the Omicron variant.

To investigate the safety, immunogenicity, and efficacy of two doses of the Pfizer vaccine administered 21 days apart in children 5 to 11 years of age.

• A phase 1, dose-finding study.
  
  • A total of 48 children 5 to 11 years of age received 10 μg, 20 μg, or 30 μg of the BNT162b2 vaccine (16 children at each dose level).
    
  • On the basis of reactogenicity and immunogenicity, a dose level of 10 μg was selected for further study
    
• In the phase 2–3,
  
  • A total of 2268 children were randomly assigned in a 2:1 ratio to receive two doses of either the BNT162b2 vaccine at 10 μg dose level or placebo.
    
  • Calculated the ratio of GMTs and the difference between the percentage of participants with seroresponse among 5-to-11-year-olds and that among 16-to-25-year-olds at 1 month after the second dose
    
  • Vaccine efficacy against Covid-19 at 7 days or more after the second dose was assessed.

• No vaccine-related serious adverse events were noted.
  
• One month after the second dose, GMT ratio neutralizing titers in 5-to-11-year-olds to those in 16-to-25-year-olds was 1.04 (95% CI, 0.93 to 1.18), a ratio meeting the prespecified immunogenicity success criterion.
  
• Covid-19 with onset 7 days or more after the second dose was reported in three recipients of the BNT162b2 vaccine and in 16 placebo recipients
  
• Vaccine efficacy is 90.7% (95% CI, 67.7 to 98.3)

A Covid-19 vaccination regimen consisting of two 10-μg doses of Pfizer administered 21 days apart was found to be safe, immunogenic, and efficacious in children 5 to 11 years of age.

Remarks:

Concomitant administration of BNT162b2 with other vaccines was not assessed, and cell-mediated responses to immunization are not yet available.

To examine reactogenicity and immunogenicity following vaccination with inactivated (CoronaVac) and vector-based (ChAdOx1-S, AZD1222) in previously infected individuals

Participant

• Participants with a prior SARS-CoV-2 infection were classified into two groups per vaccine type according to the time interval between the first date of positive SARS-CoV-2 detection and vaccination (short interval (2 to 5 months) and long interval (13 to 15 months)).
  Outcome
  
• Reactogenicity analyses were based on adverse events (AEs) within 7 d after vaccination.
  
• Binding antibody response after vaccination was compared in participants with short and long intervals since infection and in those without prior infection.
  
• Antibody function was further determined using a surrogate virus neutralization test.
  
• Total interferon-gamma response following immunization were investigated.

• Reactogenicity
  
  • Local and systemic AEs were more frequent with the first dose than with the second dose.
    
  • Most AEs were mild and moderate and were most frequent within 2 to 3 d after vaccination.
    
  • AZD1222 recipients had a higher percentage of AEs than that of CoronaVac recipients.
    
• Binding antibody responce
  
  • The anti-RBD IgG titer increased significantly and peaked at 14 d following a single dose of vaccine, compared with before vaccination.
    
  • Antibody response was greater with longer than shorter intervals.
    
  •  A single dose of vaccine in recovered individuals led to higher anti-RBD IgG levels than those of infection-naïve individuals with complete two-dose vaccination.
    
• Neutralizing activities against SARS-CoV-2 wild type and variants
  
  • Previously infected individuals had a strong response following a single dose of vaccine.Those levels of neutralizing activity were significantly higher than those in infection-naïve individuals.
    
  • In participants with prior infection, percentages of neutralizing activities in CoronaVac recipients were significantly lower than those in AZD1222 recipients.
    
  •  Neutralizing activity after vaccination was greater in participants with longer intervals than in those with shorter intervals.
    
  •  All participants who experienced infection had detectable neutralizing activity against the wild type.
    
  •  93.1% and 96.3% of individuals with short and long intervals, respectively, showed positive neutralization against B.1.1.7 following a single dose of CoronaVac. All participants vaccinated with AZD1222 had strong neutralizing activity.
    
  •  There was a decrease in SARS-CoV-2 neutralizing activity against the B.1.351 variant.
    
  •  More than 96% of individuals with previous infection had a robust increase in neutralizing antibodies against B.1.617.2 after a single dose of CoronaVac, and the percentage reached 100% for the AZD1222 vaccine.
    
  •  Neutralizing activity increased significantly after two doses of the CoronaVac vaccine. However, there was no significant increase in neutralizing activity against SARS-CoV-2 variants following the second dose of AZD1222, except against B.1.1.7.
    
•  Total interferon-gamma response
  
  • Subtracted interferon-gamma responses increased significantly 14 d after the first dose of both vaccines, compared with the baseline.
    
  • Number of seropositives was lower in CoronaVac recipients than in AZD1222 recipients.
    
  • CoronaVac recipients had a slight increase in interferon-gamma response for Ag2 after two doses of the vaccine. By contrast, level of interferon-gamma response after two doses of AZD1222 decreased significantly.

Conclusion

• The AE symptoms in previously infected individuals after vaccination were similar to those in individuals without prior infection
  
• Vaccination of individuals with prior SARS-CoV-2 infection by either inactivated or vector-based vaccine resulted in potent immune responses with titers exceeding those of unexposed individuals with two doses of vaccine.
  
• Receiving either a single dose of vector-based vaccine or two doses of inactivated vaccine can recall adequate memory for both antibody and T-cell responses in previously infected individuals.
  
• With both vaccines, a long interval between infection and vaccination led to a better immune response than that of a short interval.
  

To compare neutralization of omicron-infected cells in serum samples obtained from participants who had received 2 doses of vaccine with neutralization in samples obtained from participants who had received 3 doses

• Microneutralization assays with wild-type virus and B.1.351 (beta), B.1.617.2 (delta), and omicron variant isolates were performed with the use of serum samples obtained from two groups of 20 health care workers.
  
• One group comprised participants who had received 2 doses of Pfizer (mean, 165.6 days since receipt of the second dose), and the second group comprised those who had received 3 vaccine doses (mean, 25 days since receipt of the third dose)
  

• Receipt of 3 vaccine doses led to better neutralization of the wild-type virus and the three variants than receipt of 2 vaccine doses
  
• The third dose of Pfizer efficiently neutralized infection with the omicron variant (GMT, 1.11 after the second dose vs. 107.6 after the third dose)
  

The importance of a third vaccine dose is clear, owing to the higher neutralization efficiency against the omicron variant after the third dose than after the second dose; however, even with three vaccine doses, neutralization against the omicron variant was lower than that against the delta variant

Remarks:

1. Small sample size
2. The durability of the effect of the third dose of vaccine against Covid-19 is yet to be determined.

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Indications

For the prevention of COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older.

Dose

2 Doses

Interval

3 – 4 weeks

Contraindication

Hypersensitivity to the active substance or to any of the excipients of this vaccine

Caution

1. Do not use in people with history of severe allergic reaction from previous vaccinations
2. Do not use in people with severe allergic reactions
3. Do not use in people under 18 years old
4. Do not use in pregnant women

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Indications

1. For active immunization of individuals > 18 years old for the prevention of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2
2. Intramuscular

Dose

2 Doses

Interval

21 days

Contraindication

Hypersensitivity to the active substance or to any of the excipients of this vaccine

Caution

1. Do not use in people with history of severe allergic reaction from previous vaccinations
2. Do not use in people with severe allergic reactions
3. Do not use in people under 18 years old
4. Do not use in pregnant women

To investigate whether

1. Omicron escapes antibody neutralization elicited by the Pfizer BNT162b2 mRNA vaccine.
2. The virus still requires binding to the ACE2 receptor to infect cells.

1. Used live Omicron virus isolated in South Africa
2. Used human lung cell line clone (H1299-ACE2) engineered to express the ACE2 receptor to both isolate the virus and test neutralization
3. Tested growth in the parental H1299 which do not overexpress ACE2
4. Tested the ability of plasma from BNT162b2 vaccinated study participants to neutralize Omicron versus ancestral D614G virus in a live virus neutralization assay

1. Omicron infected the ACE2-expressing cells but did not infect the parental H1299 cells, indicating that ACE2 is required for Omicron entry.
2. Ability of plasma from BNT162b2 vaccinated study participants to neutralize Omicron showed as below;
   • Tested 14 plasma samples from 12 participants
   • Geometric mean titer (GMT) FRNT50 was 1321 for D614G.
   • Geometric mean titer (GMT) FRNT50 was 32 for Omicron (41-fold decline). However, 5 of the participants, all previously infected, showing relatively high neutralization titers with Omicron.

Previous infection, followed by vaccination or booster is likely to increase the neutralization level and likely confer protection from severe disease in Omicron infection.

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Everyone Ages 16 and Older Can Get a Booster Shot

• If you received Pfizer
  
  • Teens 16-17 years old can get a booster (Pfizer)
    
  • Adults 18 years and older should get a booster (any of the COVID-19 vaccines authorized in the US)
    
  • When to get a booster: At least 6 months after completing your primary COVID-19 vaccination series
• If you received Moderna
  •  Adults 18 years and older should get a booster (any of the COVID-19 vaccines authorized in the US)
  • When to get a booster: At least 6 months after completing your primary COVID-19 vaccination series
• If you received Janssen
  • Adults 18 years and older should get a booster (any of the COVID-19 vaccines authorized in the US)
  • When to get a booster: At least 2 months after completing your primary COVID-19 vaccination

To evaluate the protective capacity by measuring antibody-mediated neutralization efficacy against authentic SARS-CoV-2 Omicron variant

• Blood was collected from vaccinated individuals before and two weeks or three months after the double or triple Pfizer vaccines, double Moderna vaccines vs additional Pfizer booster, and heterologous AstraZeneca + Pfizer vaccines.
  
• Antibody-mediated neutralization efficacy against authentic SARS-CoV-2 Omicron was determined in vitro using an isolate from a double 1273-mRNA-vaccinated travel returnee from Zimbabwe and compared to Delta variants

The level of neutralization titers resulting in 50% virus neutralization (NT50):

• Pfizer 2 doses: against delta 47% and against omicron 0%
  
• Pfizer 3 doses: after 2 weeks – against delta 100% and against omicron 58%, after 3 months – against delta 95% and against omicron 25%
  
• For recovered people with 2 doses of Pfizer: against delta 855 and against omicron 25% (time of blood collection not mentioned)
  
• Moderna 2 doses: after 6 months – against delta 50% and against omicron 0%, 2 weeks after Pfizer booster – against delta 100% and against omicron 78%
  
• AstraZeneca+Pfizer: after 6 months – against delta 21% and against omicron 0%, 2 weeks after Pfizer booster – against delta 88% and against omicron 38%

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To evaluate SARS-CoV-2-specific humoral and cell-mediated immune responses following 2 doses of the inactivated whole-virus SARS-CoV-2 vaccine in patients with end-stage kidney disease (ESKD) receiving dialysis and compared to healthy individuals

• A prospective cohort study between April 2021 and July 2021 in Thailand among end-stage kidney disease (60 participants; 31 hemodialysis and 29 peritoneal dialysis) and healthy control (30 participants) between 18 and 59 years old
  
• Measuring anti-RBD IgG, neutralizing antibody and SARS-CoV-2 specific T cells 2 weeks after 2-dose vaccination with inactivated whole-virus SARS-CoV-2 vaccine (CoronaVac)
  

• End-stage kidney disease patients had significantly lower anti-RBD IgG (of 50 AU/ml or greater was present in 53 of 60 patients (88%) in the ESKD group VS all participants (100%) in the control group (P = 0.05).
  
• % of patients with ESKD and controls with neutralizing antibodies of 35% threshold or greater was 58% and 88%, respectively (P = 0.01).
  
• The proportion of patients with ESKD and S1-specific T cell response was comparable with controls (82% vs. 77%, P = 0.45).

The seroconversion rate and the magnitude of vaccine-elicited humoral immune response in patients with ESKD could remain suboptimal

Remarks:

Small sample size

To investigate the reactogenicity and immunogenicity of seven different COVID-19 vaccines, with three at full and half dose, as a third dose after ChAd/ChAd or BNT/BNT.

1. Participants were aged older than 30 years and were at least 70 days post two doses of ChAd or at least 84 days post two doses of BNT primary COVID-19 immunisation course
2. Participants were randomly assigned to an experimental vaccine or control to received 7 different vaccines.
3. Participants and all investigatory staff were blinded to treatment allocation.
4. Coprimary outcomes were safety and reactogenicity and immunogenicity of anti-spike IgG measured by ELISA.
5. The primary analysis for immunogenicity was on a modified intention-to-treat basis; safety and reactogenicity were assessed in the intention-to-treat population.
6. Secondary outcomes included assessment of viral neutralisation and cellular responses.

1. Three vaccines showed overall increased reactogenicity:
   • m1273 after ChAd/ChAd or BNT/BNT
   • ChAd after BNT/BNT
   • Ad26 after BNT/BNT
2. For ChAd/ChAd-primed individuals
   • Spike IgG geometric mean ratios (GMRs) between study vaccines and controls ranged from 1.8 (99% CI 1.5–2.3) in the half VLA group to 32.3 (24.8–42.0) in the m1273 group.
   • GMRs for wild-type cellular responses compared with controls ranged from 1.1 (95% CI 0.7–1.6) for ChAd to 3.6 (2.4–5.5) for m1273.
3. For BNT/BNT-primed individuals
   • Spike IgG GMRs ranged from 1.3 (99% CI 1.0–1.5) in the half VLA group to 11.5 (9.4–14.1) in the m1273 group.
   • GMRs for wild-type cellular responses compared with controls ranged from 1.0 (95% CI 0.7–1.6) for half VLA to 4.7 (3.1–7.1) for m1273.
4. Fatigue and pain were the most common solicited local and systemic adverse events, experienced more in people aged 30–69 years than those aged 70 years or older.
5. Serious adverse events were uncommon, similar inactive vaccine and control groups.

This trial has demonstrated the potential of all vaccines tested (ChAd, BNT, m1273, NVX, Ad26, CVn, and VAL) to boost immunity following an initial course of ChAd/ChAd and of six vaccines (ChAd, BNT, m1273, NVX, Ad26, and CVn) following an initial course of BNT/BNT. All vaccines showed acceptable side-effect profiles, although some schedules were more reactogenic than others.

To examine the immunogenicity and safety of different booster vaccines and reduced dosages (Sinopharm, AstraZeneca, full dose (30 μg) Pfizer, half dose (15 μg) Pfizer) in healthy adults aged 18-60 years who received a 2-dose primary series of CoronaVac or AstraZeneca vaccines.

• Prospective cohort study enrolled 352 healthy adults aged 18-60 years from March to
  September 2021.
• The eligible participants were those who have received either 2-dose CoronaVac or ChAdOx1 vaccines. The exclusion criteria were history of SARS-CoV-2 infection.

•  Overall, the adverse events for all booster vaccines were mild and moderate.
• Two weeks post-booster dose, the neutralising antibody titres against Delta variant in Sinovac-prime and AstraZeneca-prime were highest with for 30μg-BNT162b2 (411 vs 470) and 15μg-BNT162b2 (499 vs 358); followed by ChAdOx1 (271 vs 69), and BBIBP-CorV (61.3 vs 49).
• BNT162b2 also induced higher interferon gamma response.

• BNT162b2 as a booster vaccine induced the highest humoral and cellular immunity compared to BBIBP-CorV or ChAdOx1.
• An interesting observation was the higher immune responses in the CoronaVac prime group compared to the ChAdOx1-prime group when boosting with BNT162b2 at the similar interval after primary series.
• Booster vaccinations using BBIBP-CorV, ChAdOx1, BNT162b2 (standard and reduced  dosage) was safe and well tolerated
• All AEs were mild or moderate in severity and no serious AEs was reported.
• A lower dose BNT162b2 may be used as booster in settings with limited vaccine supply.

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• The recently described Omicron variant includes mutations seen in the Delta variant that are believed to increase transmissibility and mutations seen in the Beta and Delta variants that are believed to promote immune escape.The combination of mutations represents a significant potential risk to accelerate the waning of natural and vaccine-induced immunity.

3 Stratagies

1. Moderna has already tested a higher dose booster of mRNA-1273 (100 µg) in healthy adults. (from currently use of 50 µg)
2. Moderna is already studying two multi-valent booster candidates in the clinic that were designed to anticipate mutations such as those that have emerged in the Omicron variant.
3. Moderna will rapidly advance an Omicron-specific booster candidate (mRNA-1273.529). The Company has repeatedly demonstrated the ability to advance new candidates to clinical testing in 60-90 days.

To examine trends in COVID-19 incidence, morbidity and mortality in Israel since the beginning of the vaccination campaign, and discusses the impact of the new delta variant.

• A retrospective-archive study was conducted from February 27th 2020 to October 16th, 2021.
  
• Data were obtained from the Israeli Ministry of Health’s open COVID 19 database, including PCR-confirmed cases, number hospitalized – including severe cases, death rate, all by age and vaccination status, case fatality rate and changing effectiveness of the vaccine.
  
• Rates of infection and severe disease were calculated and presented per 100,000 in vaccinated and unvaccinated populations, with significant difference between rates compared using chi-squared test.

• Epidemiological data analysis
  
  • As of July 2021, the new Delta COVID variant was estimated to account for more than 90% of new cases
    
  • After three COVID waves, confirmed cases rose from under 30 new daily cases in mid-June to a high of 11,000 in early September 2021.
    
  • Severe hospitalized cases and death rates were lower than in previous waves and largely restricted to those not fully vaccinated.
    
• Changing effectiveness of Pfizer vaccine against the Delta variant
  
  • The changing effectiveness of the 2-dose Pfizer vaccine, demonstrating high effectiveness that decreased with the advent of the Delta variant in Israel.
    
  • Effectiveness against infection reduced from around 95% in February–May down to 64% in June 2021.
    
  • Effectiveness against hospitalization remained relatively high, with a small decrease from 98% in March–May to 93% in June 2021.

• In the first three months of the vaccination campaign, non-vaccinated population demonstrated much higher morbidity rates.
  
• Four months after vaccination began, low rates of infection and hospitalization in all groups was presented.
  
• Data from the fourth wave show reduced hospitalizations and mortality compared to previous waves and suggest that this may be related to high vaccine coverage
  
• Based on current data, continued effectiveness of the Pfizer vaccine – including the booster dose – against severe disease including the delta variant, and mild illness in the vast majority of cases

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• A third Pfizer vaccine dose (booster dose) provides “significant increased protection” against symptomatic disease in those aged 50 and over, irrespective of which vaccine they initially received.
• A study by the UK Health Security Agency (UKHSA) found that at least 20 weeks after being fully vaccinated with two doses of the AstraZeneca vaccine effectiveness against symptomatic disease was 44.1%, while for Pfizer it was 62.5%.
• But 2 weeks after receiving the booster dose, protection against symptomatic infection increased to 93.1% (95% CI, 91.7 to 94.3) in those who initially had two doses of the Oxford AstraZeneca vaccine, and 94.0% (95% CI, 93.4 to 94.6) for those who had Pfizer.

Remarks:

1. It is too early to know how effective the booster will be in the UK at reducing the risk of hospital admissions. But from the Israeli experience we can expect the booster to be even more effective at preventing severe disease than at preventing symptomatic infection.

2. Roll out of booster doses in the UK started in September, with those aged 50 and over, health and social care staff, at risk under 50s, over 16s living with immunosuppressed people, and those in long stay care settings being eligible.

To investigate the safety and immunogenicity of CoronaVac within the Thai population

• Prospective longitudinal cohort study at the Banphaeo General Hospital (BGH) in Samut Sakhon Province, Thailand
  
• Participants: Health care workers (HCWs) at BGH aged between 18 and 59 years, received a 2-dose regimen of CoronaVac, with a 3-week interval between doses (0–21-day schedule)
  
• Outcome
  
  •  Primary outcome: Total antibodies against receptor-binding domain (RBD) and Immunoglobulin G (IgG) antibodies against N protein
    
  • Secondary outcome:
    
    •  Local adverse reactions to the vaccine (e.g., pain, swelling, and redness)
      
    • Systemic adverse events (e.g., fever, allergic reactions, headaches, and myalgia)
      
• Time of study: Between March 1, 2021 and June 25, 2021

• Primary outcome
  
  • Total antibody against RBD
    
    • After the first CoronaVac dose
    • The seroconversion rate of total antibodies against RBD was 67%.
    • Geometric mean concentration (GMC) of 1.98 U/ml
      
    • Following CoronaVac second dose
      
    •  The seroconversion rate of total antibodies against RBD increased to 100%.
      
    • GMC of 92.9 U/ml.
      
    •  The seroconversion rates of IgG against N protein were 1% after dose 1 and 62.8% after dose 2.
      
• Secondary outcome
  
  • The overall incidence of adverse reactions was 59.5%.
    
  • Injection-site pain was the most common local adverse event (52.4%).
    
  • Myalgia was the most common systemic adverse event (31.9%).
    
  • No serious adverse events were observed.
    

• 2 CoronaVac doses administered 3 weeks apart were safe and induced a satisfactory response.
  
• Limitations:
  
  • Our examination of immunogenicity was confined to humoral immunity and did not include cellular mediated immunity.
    
  • The neutralizing capacities and the quality of the antibody responses induced by this vaccination were not assessed.
    
  • These data may not be generalizable to individuals with comorbidities or allergies.

To systematically evaluate the effectiveness and safety of the COVID-19 vaccine in the real world

1. A systematic review and meta-analysis including observational studies examining the effectiveness and safety of SARS-CoV-2 vaccines.
2. The pool vaccine effectiveness (VE) and incidence rate of adverse events after vaccination are estimated.

1. From 58 studies, 2 doses of vaccines were higher than a single dose of vaccination: 85% effective at preventing SARS- CoV-2 infections, 97% for symptomatic COVID-19, 93% for hospitalization, 96% for ICU admissions, and 95% effective for COVID-19-related death, respectively.
2. The overall pooled incidence was 0.4 per 10 000 for severe adverse events and 0.1 per 10000 for death after vaccination.

SARS-CoV-2 vaccines have reassuring safety and could effectively reduce the death, severe cases, symptomatic cases, and infections resulting from SARS-CoV-2 across the world.

To track antibody (Ab) and T cell responses after the first dose of Pfizer vaccine and compare after the second dose at 4 weeks between short and long vaccination regimens, coupling this with the protective efficacy data.

1. The study is included staff of the National Health Service hospitals, this group of participants can be represented healthy working-age group.
2. The level of Neutralizing Abs (NAbs) is assessed between the conventional regimen (3 to 4 weeks) and the extended dosing interval (6 to 14 weeks).
3. The effects of dose extension and offer immunological support are defined for decision-making.

1. According to a short interval study, vaccine effectiveness is 72% which protects against all infections by 3 weeks after dose 1 of Pfizer and maintains following the boosting the second dose.
2. The level of humoral response is induced after receiving a single dose of vaccine, although with NAbs at relatively low levels, especially against the beta and delta variants.
3. The effects of dose extension are higher levels such as IL-2-secreting, CD4+T cells in the naive group and slightly lower IFNg-secreting, CD8+T cells level.

1. Serologic response to one or two doses of Pfizer falls over time and is higher after an extended dosing interval.
2. The T-cell response remains from 1 to 13 weeks after the second dose, the result contrasts with some other studies.
3. The immunogenicity and antibody level are improved over the conventional 3-4 weeks regimen.

To assess the reactogenicity and immunogenicity of the heterologous adenoviral vector vaccine regimen (ChAdOx1-S) and the inactivated vaccine regimen (CoronaVac)

• A prospective cohort study between March 2021 and May 2021 in Thailand among adults aged ≥ 18 years old
  
• There were 4 groups, including homologous inactivated COVID-19 vaccine n=90, adenoviral vector vaccine n=90; heterologous CoronaVac followed by ChAdOx1-S n=46; and heterologous ChAdOx1-S followed by CoronaVac n=48
  
• Assessing systemic adverse events, anti-RBD-IgG, anti-N IgG, anti-S1 IgA, neutralization antibody, and SARS-CoV-2-specific T cell responses
  

• Comparable demographic data among groups
  
• The heterologous vaccination with CoronaVac followed by AstraZeneca induced higher SARS-CoV-2 RBD-specific antibody responses and neutralizing antibody against wild type and variants of concern than that of the licensed homologous CoronaVac- CoronaVac vaccination and induced similar RBD-specific binding and neutralizing antibody responses to the homologous AstraZeneca-AstraZeneca regimen
  
• Heterologous regimen led to more frequent reports of recorded adverse event symptoms than that of the homologous regimens
  

Heterologous vaccination with CoronaVac followed by AstraZeneca can be considered an alternative regimen to homologous AstraZeneca.

Remark

Durability and clinical efficacy need to be investigated

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Indications

1. For active immunization against SARS-CoV-2 Virus infection for age ≥18years
2. Intramuscular injection (IM)

Dose

2 Doses

Interval

28 days

Contraindication

Hypersensitivity to any constituents of the vaccine

Caution

1. Do not inject intravenously, intradermally or subcutaneously.
2. Those with co-morbidities
3. Thrombocytopenia and blood clotting disorders
4. Those with immunodeficiency
5. Children

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Indications:

1. U.S. FDA authorized the emergency use of the Pfizer Vaccine for the prevention of COVID-19 to include children 5-11 years of age.
2. Effectiveness: Immune responses of children 5 through 11 years of age were comparable to those of individuals 16 through 25 years of age. In addition, the vaccine was found to be 90.7% effective in preventing COVID-19 in children 5 through 11.
3. Safety: The vaccine’s safety was studied in approximately 3,100 children age 5 through 11 who received the vaccine and no serious side effects have been detected in the ongoing study.
4. The Centers for Disease Control and Prevention’s (CDC) Advisory Committee on Immunization Practices will meet next week to discuss further clinical recommendations.

To evaluate Pfizer-BioNTech vaccine effectiveness against COVID-19 hospitalization among persons aged 12–18 years

• A test-negative design
  
• Participants aged 12–18 years who were admitted to 19 pediatric hospitals during June 1–September 30, 2021
  
  • Two hospitalized case group
    • Case-patients were hospitalized with symptomatic COVID-19–like illness and a positive SARS-CoV-2 RT-PCR or antigen test result
      
    • No case-patients received a diagnosis of multisystem inflammatory syndrome in children (MIS-C) during their enrolling hospitalization
  • Two hospitalized control groups
    
    • Patients with symptoms compatible with COVID-19 with negative SARS-CoV-2 RT-PCR or antigen test results (test-negative)
      
    • Patients without COVID-19–associated symptoms who might or might not have received SARS-CoV-2 testing (syndrome-negative).
      
• Only Pfizer-BioNTech vaccine receipients were assessed in this analysis
  
• Baseline demographic characteristics, clinical information about the current illness, and SARS-CoV-2 testing history were 6. obtained through parent or guardian interviews performed.

• Among 179 COVID-19 case-patients, 6 (3%) were vaccinated and 173 (97%) were unvaccinated
  
• 77 (43%) case-patients were admitted to an intensive care unit, and 29 (16%) critically ill case-patients received life support during hospitalization
  
• The median length of hospital stay was 5 days (IQR = 2–9 days) for unvaccinated case-patients and 3 days (IQR = 2–4 days) for vaccinated case-patients.
  
• Vaccine effectiveness (VE) against COVID-19 hospitalization was 93% (95% CI = 83%–97%), during the period when B.1.617.2 (Delta) was the predominant variant.
  

During June–September 2021, receipt of 2 doses of Pfizer-BioNTech vaccine provided a high level of protection against COVID-19 hospitalization among children and adolescents aged 12–18 years in a real-world evaluation at 19 U.S. pediatric hospitals. These data suggest that increasing vaccination coverage among this group could reduce the incidence of severe COVID-19 in the United States.

Remark.

    Limitation, VE could not be assessed directly against specific variants; the predominant variant during the evaluation period was B.1.617.2 (Delta)

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• The use of a single booster dose of the Moderna COVID-19 Vaccine that may be administered at least 6 months after completion of the primary series to individual
  
  • 65 years of age and older
    
  • 18 through 64 years of age at high risk of severe COVID-19
    
  • 18 through 64 years of age with frequent institutional or occupational exposure to SARS-CoV-2
    
• The use of a single booster dose of the Janssen (Johnson and Johnson) COVID-19 Vaccine may be administered at least 2 months after completion of the single-dose primary regimen to individuals 18 years of age and older.
  
• The use of each of the available COVID-19 vaccines as a heterologous (or “mix and match”) booster dose in eligible individuals following completion of primary vaccination with a different available COVID-19 vaccine.
  
• To clarify that a single booster dose of the Pfizer-BioNTech COVID-19 Vaccine may be administered at least 6 months after completion of the primary series to individuals 18 through 64 years of age with frequent institutional or occupational exposure to SARS-CoV-2
  

To conduct an immunogenicity study among kidney transplant (KT) recipients following a full course of inactivated SARS-CoV-2 vaccine and investigate both SARS-CoV-2-specific humoral (HMI) and cell-mediated immune (CMI) responses along with the safety profile.

1. A prospective cohort study between April 2021 and July 2021
2. Seventy-five patients (37 kidney transplant [KT] recipients and 38 healthy controls) received two doses, at 4-week intervals of an inactivated SARS-CoV-2 vaccine.
3. SARS-CoV-2-specific humoral (HMI) and cell-mediated immunity (CMI) were measured before, 4 weeks post-first dose, and 2 weeks post-second dose.
4. The median (IQR) age of KT recipients was 50 (42–54) years and 89% were receiving calcineurin inhibitors/mycophenolate/corticosteroid regimens.
5. The median (IQR) time since transplant was 4.5 (2–9.5) years

1. Among 35 KT patients, the median (IQR) of anti-RBD IgG level measured by CLIA after vaccination was not different from baseline, but was significantly lower than in controls (2.4 [1.1–3.7] vs. 1742.0 [747.7–3783.0] AU/ml, p < .01)
2. Percentages of neutralizing antibody inhibition measured by surrogate viral neutralization test (0% [0–0] vs. 71.2% [56.8–92.2], p < .01)
3. The median (IQR) of SARS-CoV-2 mixed peptides-specific T cell responses measured by ELISpot was significantly increased compared with baseline (30 [4–120] vs. 12 [0–56] T cells/106 PBMCs, p = .02) and not different from the controls
4. Only minimal and mild adverse reactions were observed

KT recipients develop weak antibody responses and their neutralizing effect to the spike protein, but with potentially optimal SARS-CoV-2-specific T cell responses after completing a two-dose course of inactivated SARS-CoV-2 vaccine with acceptable adverse reactions and favorable short-term outcomes

To investigate the effectiveness of heterologous ChAdOx1 nCoV-19 and mRNA prime-boost vaccination against symptomatic Covid-19 infection in Sweden

•  A study cohort including:
  
  • 94,569 individuals that had received heterologous AstraZeneca/Pfizer prime-boost vaccination
    
  • 16,402 individuals that received heterologous AstraZeneca/Moderna prime-boost vaccination
    
  • 430,100 individuals that received homologous AstraZeneca/AstraZeneca prime-boost vaccination
    
• 180,716 individuals were selected who were unvaccinated at the date of vaccination in the corresponding case.
  
• Baseline was the date of the second dose of any vaccine, with the same date in the corresponding unvaccinated individual.
  
• The outcome included incident symptomatic Covid-19 infection occurring >14 days after baseline.
  

• The symptomatic Covid-19 infection was confirmed in 187 individuals with heterologous vaccine schedules (incidence rate: 2.0/100,000 person-days) and in 306 individuals from the unvaccinated control group (incidence rate: 7.1/100,000 person-days)
  
• The adjusted vaccine effectiveness was
  
  • 67% (95% CI, 59-73, P<0.001) for heterologous AstraZeneca/Pfizer prime-boost vaccination
    
  •  79% (95% CI, 62-88, P<0.001) for heterologous AstraZeneca/Moderna prime-boost vaccination
    
• When combined and analysed together, the two heterologous vaccine schedules had an effectiveness of 68% (95% CI, 61-74, P<0.001) which was significantly greater (Pinteraction<0.001) than the 50% effectiveness for AstraZeneca/ AstraZeneca (95% CI, 41-58, P<0.001).
  

The findings of this study suggest that the use of heterologous ChAdOx1 nCoV-19 and mRNA prime-boost vaccination is an effective alternative to increase population immunity against Covid-19, including against the Delta variant which dominated the confirmed cases during the study period.

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Indications

Active immunization of individuals ≥ 18 years old for the prevention of coronavirus disease 2019

Dose

2 Doses

Interval

4 – 12 weeks

Contraindication

Hypersensitivity to the active substance or to any of the excipients and patients who have experienced major venous and/or arterial thrombosis in combination with thrombocytopenia following vaccination with any COVID-19 vaccine.

Caution

Hypersensitivity including anaphylaxis

Remarks

“All batches of AstraZeneca’s COVID-19 vaccine produced at Siam Bioscience, undergo stringent quality testing and are also authorised by regulators and international laboratories in Europe and the U.S.” said Nualphan Lamsam, Honorary Director of Corporate Communications, Siam Bioscience Co., Ltd.

To assess the effectiveness of vaccination in preventing severe forms of Covid-19, EPI-PHARE carried out two real-life studies in parallel using data from the SNDS (National Health Data System)

• The cohort of 22.6 million people over the age of 50 from the national database pseudonymized VAC-SI and the national health data system (SNDS).
  
• Each vaccinated subject was chronologically matched (from February 1 to April 30, 2021) to the date of vaccination (or index date) to an unvaccinated subject of the same age, sex and administrative region.
  
• Reducing the risk of severe forms of Covid-19 after 14^th days of second dose injection
  
• The efficacy was estimated specifically during the period of start of circulation of the Delta variant in France, between June 20 and July 20, 2021.

• Vaccine effectiveness
  
  • An overall reduction for all vaccines the risk of hospitalization from COVID-19 was 92% (95% CI, 91% to 94%)
    
  • A reduction in the risk of death during hospitalization from Covid-19 86% (95% CI, 78% to 91%) at 14 days after injection of the second dose.
    
  • The effectiveness on severe forms of Covid-19 did not seem to decrease over the available follow-up period of up to 5 months.
    
  • In the cohort aged 75 and over, it was 94% to 5 months of follow-up for Pfizer vaccine
    
  • In the cohort aged 50 to 74, it was 97% at 4 months of follow-up for Pfizer vaccine
    
• For the impact of the Delta variant, the reduction in the risk of hospitalization for Covid-19 were estimated.
  
  • In the cohort aged 75 and over, the efficacy was 84% (95% CI, 75% to 90%)
    
  • In the cohort aged 50 to 74 92%, the efficacy was (95% CI, 89% to 95%)
    

• All Covid-19 (studied) vaccines are highly effective and have a major effect on reducing the risk of severe forms of Covid-19 in people aged 50 and over in France in real life. Continuing monitoring by PPE-PHARE will make it possible to measure the evolution of efficiency over a longer period and better characterize the effects of the Delta variant.

Remarks:

1. For Moderna and AstraZeneca vaccines, follow-up was too short to be able to study their effect at 4 or 5 months.
2. The impact of the Delta variant, the reduction in the risk of hospitalization for Covid-19 was estimated specifically during the period of the start of the circulation of the Delta variant in France, between June 20 and July 20, 2021.

To estimate the reduction in the rates of confirmed infection and severe disease among booster recipients

•  A cross-sectional observational study from medical data from the Ministry of Health database that were extracted on September 2, 2021
  
• 1,137,804 participants included for analysis
  
• Israeli residents who were 60 years of age or older had been fully vaccinated at least 5 months earlier
  
• Study period July 30, 2021 to August 31, 2021 for confirmed infection and August 26, 2021 for severe illness
  

• The rate of confirmed infection was lower in the booster group than in the non-booster group by a factor of 11.3
  
• The absolute between-group difference in the rate of confirmed infection was 86.6 infection per 100,000 person-days
  
• The rate of severe illness was lower in the booster group than in the non-booster group by a factor of 19.5
  
• The absolute between-group difference in the rate of severe illness was 7.5 infection per 100,000 person-days
  

A booster dose of the BNT162b2 vaccine reduced the rates of both confirmed infection and severe COVID-19 illness in a large Israeli population of participants who were 60 years of age or older.

To evaluate the efficacy of COVID-19 vaccines from the perspective of overall infection, severe infection, and fatal infection, following receipt of 3 types of vaccines: messenger RNA (mRNA)-based vaccine; viral vector (non-replicating) vaccine; and inactivated vaccine

• Meta-analysis comprised of 7 clinical trials
• 3 categories of vaccine (comprising 6 different vaccines)
• 504,781 cases
• Outcome: efficacy of COVID- 19 vaccines against overall infection, severe infection, and fatal infection

• Efficacy of COVID- 19 vaccines against overall infection by the delta variant
  • 59% for inactivated vaccines
  • 67.2% for viral vector vaccines
  • 77.74% for mRNA-based vaccines
• Efficacy of COVID- 19 vaccines against severe infection (defined as per World Health Organization guidelines)
  • 70.2% for inactivated vaccines
  • 95% for viral vector (non-replicating) vaccines
  • 89.25% for mRNA-based vaccines
• The incidence of death in the entire vaccinated group (inactivated vaccines and mRNA-based vaccines) was 0%.

• In term of efficacy against overall infection by the delta variant, mRNA-based vaccines ranked first, followed by viral vector (non-replicating) vaccines and inactivated vaccines, which is consistent with the results against the original SARS-CoV-2 strain.
• The efficacy of all COVID- 19 vaccines has dropped against the delta variant.

To report on the adverse events after the first dose of Sinopharm vaccine on 583 Iranian MS patients

• A Google form link was sent to MS patients through social networks, between May 1, 2021 and May 22, 2021.
  
• As the main vaccine for this population was Sinopharm, those patients who got other vaccine types were excluded.

• At least one complaint was reported by 350 (60%) of vaccine recipients.
  
  • Constitutional complaints (malaise, fatigue, fever, shivering, & generalized body pain) were reported by 299 (51%) cases .
    
  • Headache was the next most-reported symptom (n= 55,9%).
    
• Worsening MS or MS attack
  
  • 2 (0.3%) patients complained of worsened MS symptoms
    
  • 5 (0.9%) patients reported MS attacks

• No serious adverse event was found.
• Only five recipients (0.9%) reported MS relapse after vaccination. MS worsening was a minor incident related to fever.

To evaluate safety and immunogenicity of an inactivated recombinant Newcastle Disease Virus Vaccine expressing SARS-CoV-2 spike

Phase 1 segment of a randomized, observer-blind, placebo-controlled, phase 1/2 trial conducted in healthy adults 18-59 years, receiving inactivated recombinant Newcastle Disease Virus Vaccine expressing SARS-CoV-2 spike between March 22 and April 23, 2021

• 210 healthy adults (5 excluded)
  
• Most solicited injection site and systemic reactogenicity during 7 days after each vaccination was mild and transient.
  
• Ranking of immunogenicity with the 10 µg formulation performing best followed by the 3 µg + 1.5 µg CpG1018 adjuvant, 3 µg, 1 µg + 1.5 µg CpG1018 adjuvant, and 1 µg formulations
  

• NDV-HXP-S had an acceptable safety profile and potent immunogenicity in this clinical trial phase 1
  
• The vaccine was immunogenic in a formulation and dose dependent manner, inducing levels of vaccine-homologous anti-S IgG and virus neutralizaing antibodies that exceeded by several fold the levels measured in 14-day convalescent sera from consecutive cases of mild to moderate COVID-19 illness in 2020
  
• The 3 µg S + 1.5 µg CpG1018 adjuvant formulations were selected for further assessment in the phase 2 of the ongoing clinical trial
  

To report the vaccine efficacy and safety results of the final analysis of the blinded phase of the trial

• The interim analysis in phase 3, observer-blinded, placebo-controlled clinical trial
• 30,415 adult volunteers who were at high risk for Covid-19 or its complications were randomly assigned in a 1:1 ratio to receive 2 doses of the mRNA-1273 vaccine and placebo
• Stratified according to age and Covid-19 complications risk criteria (≥18 to <65 years and not at risk, ≥18 to <65 years and at risk, and ≥65 years)
• The primary outcome was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2
• The data cutoff date was March 26, 2021
  

• The efficacy in preventing illness was 93.2%, with 55 confirmed cases in the mRNA-1273 group, and 744 in the placebo group
• The efficacy in preventing severe disease was 98.2%, with 2 cases in the mRNA-1273 group and 106 in the placebo group
• The efficacy in preventing asymptomatic infection starting 14 days after the second injection was 63.0%, with 214 cases in the mRNA-1273 group and 498 in the placebo group.
• Vaccine efficacy was consistent across ethnic and racial groups, age groups, and participants with coexisting conditions.
• No safety concerns were identified.
  

The mRNA-1273 vaccine continued to be efficacious in preventing Covid-19 illness and severe disease at more than 5 months, with an acceptable safety profile, and protection against asymptomatic infection was observed

Remarks:

Limitations
1. At the trial design stage in early 2020, the efficacy and safety of the mRNA-1273 vaccine were unknown; for that reason, certain key populations such as pregnant women, children, and immunocompromised persons were not included in the trial.
2. Given the period during which the blinded phase of the trial was conducted, assessment of vaccine efficacy in preventing Covid-19 caused by SARS-CoV-2 variants of concern is limited

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• Johnson & Johnson single-shot vaccine showed strong and long-lasting protection against
  
  • 79 % (CI, 77%-80%) for infections and 81 % (CI, 79%-84%) for hospitalizations
    
  • No evidence of reduced effectiveness over the study duration
• Phase 3 trial
  
  • 75 % (CI, 65%-82%) against severe/critical
    
  • 74 % efficacy in the U.S. against severe/critical (CI, 39%-91%)
    
  • 89 % against hospitalization (CI, 24%-100%)
    
  • 83 % against COVID-19-related death (CI, 41%-97%)
• Booster shot at two months provided 94 % protection against COVID-19 in the U.S.
  
  • 100 % (CI, 33%-100%) against severe/critical COVID-19 – at least 14 days post-final vaccination
    
  • 75 % against symptomatic (moderate to severe/critical) globally (CI, 55%-87%).
    
  • 94 % against symptomatic (moderate to severe/critical) in the U.S. (CI, 58%-100%)
• Booster shot at six months provided 12-fold increase in antibodies
  • Antibody levels increased 9-fold a week after the booster and continued to climb to 12-fold higher 4 weeks after the booster. All rises were irrespective of age

To compared the antibody recognizing the receptor binding domain of the spike (S), glycoprotein (IgG‐S),and nucleocapsid protein (IgG‐N) of SARS CoV‐2 titers to investigate the interplay between humoral immune responses in 68 HCWs

Randomly selected 45 HCWs who had no previous infection were enrolled in this study. Compared the Receptor-binding Domain of the spike (S) glycoprotein (IgG‐S) and nucleocapsid protein (IgG‐N) of SARS CoV‐2. First antibody measurement 1 month after administering second CoronaVac (booster1) dose and second antibody titers were measured 1 month after third (booster2) dose by using Abbott Architect i2000 (Abbott Laboratories)

IgG‐S levels for three times CoronaVac vaccinated and inoculated with BNT162b2 jab as the third vaccine dose groups approximately 6 months after the application of their first CoronaVac as well as IgG‐N titers for both groups showed statistically significant differences. IgG‐S and IgG‐N titers in the three times CoronaVac vaccinated group of HCW presented a high Spearman’s correlation value, but correlation coefficient between IgG‐S and IgG‐N titers in BNT162b2 jab as the third vaccine dose was negligible. IgG‐S titers were substantially higher in inoculated with BNT162b2 jab as the third dose than those the three times CoronaVac vaccinated and healthy controls group. Median values of IgG‐N titers were higher in 3 times CoronaVac vaccinated group than those HCWs of the other two groups

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To assess the effect of SARS-CoV-2 variants B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.429 (Epsilon), B.1.526 (Iota), and B.1.617.2 (Delta) on binding, neutralizing, and angiotensin-converting enzyme 2 (ACE2)-competing antibodies elicited by the messenger RNA (mRNA) vaccine mRNA-1273 over 7 months

Investigate the effect of SARS-CoV-2 variants on recognition by sera from individuals who received two 100-mg doses of the SARS-CoV-2 vaccine mRNA-1273 administered as a two-dose series, 28 days apart.

• Low-level recognition of all variants was observed after a single dose
• Activity against all variants peaked 2 weeks after the second dose, with moderate declines over time through day 209.
• The neutralizing activity (pseudovirus assay) was highest against D614G and lowest against B.1.351, with values for all other variants tested falling between those 2 variants.

• mRNA-1273-elicited antibody activity against SARS-CoV-2 variants persisted 6 months after the second dose, albeit at reduced levels compared with peak activity, with more than half of subjects maintaining neutralizing activity against B.1.351 at the latest time point tested.
• High levels of binding antibodies recognizing all tested variants were maintained in all subjects over this time period.
  

To assess the vaccine effectiveness (VE) of Moderna, Pfizer, and Janssen vaccines in preventing COVID-19 hospitalizations

A case-control analysis among adults without immunocompromising conditions aged ≥ 18 years old who were hospitalized at 21 U.S. hospitals across 18 states during 11 March-15 August 2021

• Vaccine effectiveness after full vaccination from Moderna, Pfizer-BioNTech and single-dose Janssen during full surveillance period was 93%, 88%, and 77%, respectively.
• Person vaccinated with Janssen vaccine also had lower post-vaccination anti-SARS-CoV-2 antibody levels than did recipients of mRNA vaccines.
  

Remarks:

An immunologic correlate of protection has not been established for COVID-19 vaccines

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To report the full set of safety and immunogenicity data for BBIBP-CorV in phase 1 and 2 clinical trials among healthy people younger than 18 years in China

• Randomised, double-blind, controlled, phase 1/2 trial
  
• Participant: Healthy individuals aged 3–17 years
• Intervention: BBIBP-CorV vaccine on a three-dose schedule (on days 0, 28, and 56)
  
• Control: Saline and aluminium hydroxide adjuvant on a three-dose schedule (on days 0, 28, and 56)
• Outcome:
  
  • The primary outcome: Safety
    
  • The secondary outcomes: Immunogenicity

• Primary outcome
  • The most common injection site adverse reaction was pain.
  • The most common systematic adverse reaction was fever.
  • Adverse reactions were mostly mild to moderate in severity.
• Secondary outcome
  
  • The neutralising antibody GMT against the SARS-CoV-2 virus on day 28 after the second vaccination
    • 105.3-180.2 in the 3–5 years cohort
      
    • 84.1-168.6 in the 6–12 years cohort
    • 88.0-155.7 in the 13–17 years cohort
  • The neutralising antibody GMT against the SARS-CoV-2 virus on day 28 after the third vaccination
    • 143.5 – 224.4 in the 3–5 years cohort
    • 127 – 184.8 in the 6–12 years cohort
    • 150.7 – 199 in the 13–17 years cohort

• The inactivated COVID-19 vaccine BBIBP-CorV is safe and well tolerated at all tested dose levels in participants aged 3–17 years.
• BBIBP-CorV elicited robust humoral responses against SARS-CoV-2 infection after two doses.
• Limitation
  • Short duration of follow-up (84 days)
  • Limited racial and ethnic diversity
  • Cellular immunity was not evaluated.
  • Absence of data for cross-protection efficacy of neutralising antibody against newly emerged variants.

To assess the safety and immunogenicity of BBIBP-CorV vaccine in participants aged 3–17 years.

• A randomised, double-blind, controlled, phase 1/2 trial
• Stratified participants to age (3–5, 6–12, or 13–17 years) and dose group
• Randomly assigned, using stratified block randomisation (block size eight), to receive three doses of 2, 4, or 8 μg of vaccine or control (1:1:1:1) 28 days apart
  

• The most common injection site adverse reaction
  • Pain: 9.1% in all vaccination groups; 7.9% in vaccination groups of the 13–17 years and 1.2% in the control group of the 6–12 years;)
• The most common systematic adverse reaction
  • Fever: 12.7% in all vaccination groups and 7.1% in the control group of the 3–5 years; 5.2% in the vaccination groups and 1.2% in the control group of the 6–12 years; 10.3% in all vaccination groups and 9.5% in the control group of the 13–17 years)
• Adverse reactions were mostly mild to moderate in severity.
• The neutralising antibody GMT against the SARS-CoV-2 virus
  • Ranged from 105.3-180.2 in the 3–5 years, 84.1-168.6 in the 6–12 years, and 88.0-155.7 in the 13–17 years on day 28 after the second vaccination
  • Ranged from 143.5-224.4 in the 3–5 years, 127-184.8 in the 6–12 years, and 150.7-199 in the 13–17 years on day 28 after the third vaccination.
    

• 3-dose of BBIBP-CorV inactivated vaccine had an acceptable safety profile, and was able to elicit robust humoral response against SARS-CoV-2 in participants younger than 18 years
• Adverse reactions occurred predominantly after the first dose and showed similar frequency in participants aged 3–17 years and aged 18–59 years or 60 years or older
• The most common adverse reactions were pain and fever, which were transient or resolved in few days
  

Remarks:

Limitations

1. short duration of follow-up (84 days), safety profile
2. participants had limited racial and ethnic diversity
3. Cellular immunity elicited by BBIBP-CorV, especially T-cell response, was not evaluated
4. An absence of data for cross-protection efficacy of neutralising antibody elicited in the cohort aged 3–17 years against newly emerged variants (eg, B.1.1.7 and B.1.617)
5. The neutralising antibody elicited by BBIBP-CorV could inhibit SARS-CoV-2 infection in cell culture, but the protection efficacy in people younger than 18 years is unknown.

To report the safety and immunogenicity of the hetrologous prime-boost immunization with inactivated SARS-CoV-2 vaccine (CoronaVac) and a recombinant adenovirus type-5-vectored COVID-19 vaccine (Convidecia) in Chinese adults at 18-59 years of age

• randomized, controlled, observer-blinded trial in healthy adults 18-59 years of age primed with one or two doses of CoronaVac
• Intervention: booster dose of Convidecia or CoronaVac
• Outcome: safety and immunogenicity

• In both two-dose and three-dose regimen cohorts, Convidecia recipients reported more adverse reactions than CoronaVac recipients. The adverse reactions were generally mild to moderate.
• The heterologous immunization with Convidecia induced higher live viral neutralizing antibodies than did the homogeneous immunization with CoronaVac.

The heterologous prime-boost regimen with Convidecia after the priming with CoronaVac was safe and significantly immunogenic than a homogeneous boost with CoronaVac

To evaluate immune response among vaccinees who had received Sinovac followed by AstraZeneca (~4 weeks apart)

• Participant: Vaccinees who had received Sinovac followed by AstraZeneca (~4 weeks apart) at King Chulalongkorn Memorial Hospital in Bangkok
• Outcome: SARS-CoV-2 anti-S antibodies

• The mean antibody level among the Sinovac-AstraZeneca vaccinees (797 U/mL; 95% CI: 598.7-1062) was comparable to that of vaccinees who received two- dose AstraZeneca (818 U/mL; 95% CI: 662.5-1010), which was not a significant difference (p=0.49).
  
• The geometric mean antibody titer among the two-dose Sinovac vaccinees was 96.4 U/mL (95% CI: 76.1-122.1), which was not significantly more than the mean of 78 U/mL (95% CI: 52.8-115.8) observed among convalescent individuals (p=0.68).

The heterologous prime-boost with Sinovac followed by AstraZeneca may provide better antibody response than two doses of Sinovac and induce similar levels of antibody induction as elicited by two doses of AstraZeneca.

To evaluate 8-month durability of humoral and cellular immune responses after Ad26.COV2.S vaccination

• Intervention: Ad26.COV2.S vaccine in one or two doses
• Comparison: Placebo
• Outcome:
  • Antibody and T-cell
  • Neutralizing antibody responses against the parental WA1/2020 strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the SARS-CoV-2 variants.
    

• The median binding antibody titer against the WA1/2020 receptor-binding domain was
  • 645 on day 29
  • 1306 on day 239
• T-cell response
  • The median CD8+ T-cell response was 0.0545% on day 57 and 0.0734% on day 239
  • The median CD4+ T-cell responses were 0.0435% on day 57 and 0.0176% on day 239
• Median pseudovirus neutralizing antibody titers to SARS- CoV-2 (on day 29 / on day 239)
  • W A1/2020: 272/184
  • D614G: 167/158
  • B.1.1.7 (ALPHA): 60/147
  • B.1.617.1 (KAPPA): 49/171
  • B.1.617.2 (DELTA): 39/107
  • P.1 (GAMMA): 28/129
  • B.1.429 (EPISLON): 27/87
  • B.1.351 (BETA): <20/62
    

• Ad26.COV2.S vaccine elicited durable humoral and cellular immune responses with minimal decreases for at least 8 months after immunization.
• We observed an expansion of neutralizing antibody breadth against SARS-CoV-2 variants over this time period.

To estimate the effectiveness of an inactivated SARS-CoV-2 vaccine in Chile

A prospective observational national cohort study in Chile in adults aged 16 years of age or older who were affiliated with the public national health care system from 2 February to 1 May 2021 to estimate the vaccine effectiveness of inactivated SARS-CoV-2 vaccine (CoronaVac)

There were 10,187,720 eligible participants in the study. Two-dose adjusted vaccine effectiveness for laboratory-confirmed COVID-19 was 65.9%, for admission to the ICU for COVID-19 was 90.3% and for COVID-19 related death was 86.3%.

The CoronaVac vaccine was highly effective in protecting against severe COVID-19 disease and death

Remarks:

• Observational with short follow-up
• The national genomic surveillance for SARS-CoV-2 in Chile has reported the circulation of at least 2 viral lineages of variants of concern: P.1 and B.1.1.7. Yet, there was no representative data to estimate vaccine effectiveness on variants.
  

• To describe individual risk factors associated with SARS-CoV-2 infection at least 14 days after first vaccination or 7 days after second vaccination
  
• To assess illness duration, severity, and symptom profile in individuals with SARS-CoV-2 infection after their first and second vaccinations, compared with unvaccinated individuals with SARS-CoV-2 infection.
  

• A prospective, community-based, nested, case-control study, 1:1 ratio
  
• Using data from UK-based, adult (≥ 18 years) participants of the COVID Symptom Study logged through a mobile phone app between Dec 8, 2020 and July 4, 2021.
  
• Describe individual risk factors associated with SARS-CoV-2 infection at least 14 days after first vaccination or 7 days after second vaccination
  
• Assess illness duration, severity, and symptom profile in individuals with SARS-CoV-2 infection after their first and second vaccinations, compared with unvaccinated individuals with SARS-CoV-2 infection.
  

• Case 1 = 6,030 (0.5%) of 1,240,009 app users
  
• Case 2 = 2,370 (0.2%) of 971,504 app users
  
• The odds of post-vaccination infection following the first dose were increased in frail, older adults, and those living in more deprived area, and were decreased with individuals without obesity
  
• Compared to unvaccinated controls, after their second vaccine dose, individuals were less likely to have prolonged illness (symptoms ≥ 28 days), more than 5 symptoms in the first week of illness, or present to hospital.
  
• Most symptoms were less common in vaccinated versus unvaccinated participants
  
• Fully vaccinated individuals with COVID-19 were more likely to be completely asymptomatic than were unvaccinated controls
  

All Covid-19 (studied) vaccines are highly effective and have a major effect on reducing the risk of severe forms of Covid-19 in people aged 50 and over in France in real life. Continuing monitoring by PPE-PHARE will make it possible to measure the evolution of efficiency over a longer period and better characterize the effects of the Delta variant.

Remark :

An observational rather than a formal comparison

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*Update October 20, 2021: The FDA expands authorizations for COVID-19 vaccine booster doses for eligible populations who received the Pfizer or Moderna or Janssen COVID Vaccine recipients 18 and older.

**Please see the updated resource links or go to the date October 21, 2021 on this website

Indications:

1. FDA approved COVID-19 vaccine for the prevention of COVID-19 in individuals 16 years of age and older
2. The vaccine continues to be under emergency use authorization for:
   1. individuals 12 years of age and older
   2. a third dose in certain immunocompromised people
   3. a single booster dose in people 65 years of age and older
   4. a single booster dose in people 18 through 64 at high risk of severe COVID-19
   5. a single booster dose in people 18 through 64 years of age with frequent institutional or occupational exposure to SARS-CoV-2
      

Dose: 2 Doses

Interval: 3 weeks

Contraindication: Known history of a severe allergic reaction (e.g., anaphylaxis) to any component of COMIRNATY

Caution:

1. Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days following the second dose.
2. Fainting may occur in association with administration of injectable vaccines, including COMIRNATY. Procedures should be in place to avoid injury from fainting.
3. The most common reported adverse reactions in clinical studies (≥10%)
   1. 16-55 years old: pain at the injection site (88.6%), fatigue (70.1%), headache (64.9%), muscle pain (45.5%), chills (41.5%), joint pain (27.5%), fever (17.8%), injection site swelling (10.6%)
   2. ≥ 56 years old: pain at the injection site (78.2%), fatigue (56.9%), headache (45.9%), muscle pain (32.5%), chills (24.8%), joint pain (21.5%), injection site swelling (11.8%), fever (11.5%), injection site redness (10.4%)

Remarks:

There are no data available on the interchangeability of this vaccine with other COVID-19 vaccines to complete the vaccination series. Those received the first dose of COMIRNATY should receive COMIRNATY as a second dose.

To evaluate the safety, tolerability, and reactogenicity of escalating doses of the ChulaCov19 vaccine

Escalating doses (10 µg, 25 µg, and 50 µg) of the ChulaCov19 vaccine, administered intramuscularly (IM) according to a repeat vaccination schedule (given 21 days apart) in healthy adults aged 18-55 years and in elderly adults aged 56-75 years

– High level of immunogenicity against COVID-19 in the participants and present T-cells immunogenicity against COVID-19 variants
– The vaccine has the protection level against the wild type including the four variants: alpha, beta, gamma and delta
– After 7 days, the adverse events are mild to moderate. Most often after the second dose of vaccination for ex. pain at injection site, fatigue, fever, chills. All recover within a few days.

• Can be stored at refrigerator temperature (2-8°C) for up to 3 months and storage temperature (25°C) for 2 weeks, making it easier to store than other mRNA vaccines.
  
• The test results in mice were very good. The vaccine can prevent illness, stop the infection from covid-19 getting into the bloodstream and reduce the number of viruses in the nose and lungs and is safe from the toxicity test results.
• Can be produced quickly because mRNA vaccines do not need to be cultured, only knowing the strain of the virus can produce a vaccine. It doesn’t require large factories and, if mutated, in the future it can synthesize new vaccines very quickly.

To estimate vaccine effectiveness against SARS-CoV-2 infection and against any severe, critical, or fatal COVID-19 disease

• Matched test-negative, case-control study design in resident population of Qatar
• Outcome: vaccine effectiveness against SARS-CoV-2 infection and against any severe, critical, or fatal COVID-19 disease

• Effectiveness against any SARS-CoV-2 infection (symptomatic or asymtomatic)
  
  • 0% in first two weeks after the first dose
    
  • 36.5% (95% CI: 33.1-39.8) in the third week after the first dose
    
  • peak of 72.1% (95% CI: 70.9- 73.2) in the first five weeks after the second dose
    
  • decline accelerating ≥15 weeks after the second dose
  • 0% after 20 weeks after the second dose
• Effectiveness against symptomatic infection was higher than against asymptomatic infection, but stiil waned in the same fashion.
• Effectiveness against any severe, critical, or fatal disease
  
  • 67.7% (95% CI: 59.1-74.7) in the third week after the first dose
    
  • peak of 95.4% (95% CI: 93.4-96.9) in the first five weeks after the second dose
    
  • There was no evident decline in this effectiveness over time.

BNT162b2-induced protection against infection appears to wane rapidly after its peak right after the second dose, but it persists at a robust level against hospitalization and death for at least six months following the second dose.

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1. The U.S. Food and Drug Administration approved the first COVID-19 vaccine, the Pfizer-BioNTech COVID-19 Vaccine, will now be marketed as Comirnaty, for the prevention of COVID-19 disease individuals 16 years and older.
2. Under emergency use authorization (EUA), including for individuals 12 through 15 year of age and for the administration of a third dose in certain immunocompromised individuals
3. Comirnaty contains messenger RNA (mRNA), a kind of genetic material. The mRNA is used by the body to make a mimic of one of the proteins in the virus that cause COVID-19. The mRNA in Comirnaty is only present in the body for a short time and is not incorporated into – nor does it alter – an individual’s genetic material.
4. Based on results from the clinical trial, the vaccine was 91% effective in preventing COVID-19 disease.
5. The safety of Comirnaty was evaluated in approximately 22,000 people who received the vaccine and 22,000 people who received a placebo 16 years of age and older.
6. The most commonly reported side effects by those clinical trial participants who received Comirnaty were pain, redness and swelling at the injection site, fatigue, headache, muscle or joint pain, chills, and fever.
7. The post-authorization safety surveillance data pertaining to myocarditis and pericarditis: The observed risk is higher among males under 40 years of age compared to females and older males. The observed risk is highest in males 12 through 17 years of age. Available data from short-term follow-up suggest that most individuals have had resolution of symptoms. However, some individuals required intensive care support. Information is not yet available about potential long-term health outcomes. The Comirnaty Prescribing Information includes a warning about these risks.
8. The FDA is requiring the company to conduct postmarketing studies to further assess the risks of myocarditis and pericarditis following vaccination with Comirnaty.
9. The company has committed to additional post-marketing safety studies, including conducting a pregnancy registry study to evaluate pregnancy and infant outcomes after receipt of Comirnaty during pregnancy.

To estimate the effectiveness of the inactivated whole virus vaccine, CoronaVac (Sinovac Biotech), against symptomatic covid-19 in the elderly population of São Paulo state, Brazil during widespread circulation of the gamma variant

• Test negative case-control study in adult aged ≥ 70 years with covid-19-like illness
• Intervention: vaccination with two dose regimen of CoronaVac
• Outcome: Vaccine effectiveness against symptomatic covid-19, covid-19 associated hospital admissions, deaths with covid-19
  

• Vaccine effectiveness in adults aged ≥70 years against symptomatic covid-19 after second dose is 46.8 %, against covid-19 associated hospital admissions after second dose: 55.5 %, against deaths with covid-19 after the second dose: 61.2 %
• Vaccine effectiveness was observed to decline with increasing age.

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To evaluate the safety, immunogenicity, and efficacy of the mRNA-1273 SARS-CoV-2 vaccine in adolescent

• Phase 2–3, placebo-controlled trial, healthy adolescents (12 to 17 years of age)
• Intervention: two injections of the mRNA-1273 vaccine (100 μg in each) administered 28 days apart
• Comparison: two injections of saline administered 28 days apart
• The primary objectives: evaluation of the safety of mRNA-1273 in adolescents and the noninferiority of the immune response in adolescents as compared with that in young adults (18 to 25 years of age) in a phase 3 trial

• mRNA-1273 group, the most common solicited adverse reactions after the first or second injections were
  – Injection-site pain (in 93.1% and 92.4%, respectively)
  – Headache (in 44.6% and 70.2%, respectively)
  – Fatigue (in 47.9% and 67.8%, respectively)
• No serious adverse events related to mRNA-1273 were noted.
• The geometric mean titer ratio of pseudovirus neutralizing antibody titers in adolescents relative to young adults was 1.08 (95% confidence interval [CI], 0.94 to 1.24).
• The absolute difference in serologic response was 0.2 percentage points (95% CI, −1.8 to 2.4), which met the noninferiority criterion.
  

The immunogenicity of mRNA-1273 in adolescents was noninferior to that in young adults in the phase 3 trial, with a similar safety profile.

Aimed to provide evidence on Sinopharm COVID-19 vaccine side effects

A cross-sectional survey study was conducted to collect data on the effects of the COVID-19 vaccine among individuals in the United Arab Emirates. Demographic data, vaccination and the response of people unwilling to take the COVID-19 vaccine were reported

• Side effects post first dose of normal injection site pain, fatigue and headache were more common in participants aged ≤49 years versus > 49 years, while pain at the vaccination site, fatigue, lethargy, headache and tenderness were the most common side effects post second dose in both groups.
• All side effects for both doses were more prevalent among participants aged ≤49 years. Side effects were more common in females compared with males for both doses.
• The most common reason for being unwilling to take the vaccine was that vaccines are not effective.

Post-vaccination side effects for the first and second doses were mild and predictable, and there were no hospitalization cases; this data will help reduce vaccine hesitancy.

To compare humoral/cellular immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA

An observational study including 216 immunocompetent individuals. Comparing spike-specific Ig neutralizing antibodies; spike-specific CD4+ and CD8+ T-cell responses at 14 days after vaccination among heterologous ChAdOx1 nCoV-19/mRNA vaccination and homologous regimens.

The heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost and higher or comparable in magnitude to homologous mRNA vaccine regimens

Heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.

Remarks:

No immune-based correlates of protection

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Indications

Active immunization to prevent COVID-19 caused by SARS-CoV-2 virus, in individuals 12 years of age and older.

Dose

2 Doses

Interval

3 weeks

Contraindication

Hypersensitivity to the active substance or to any of the excipients listed

Caution

1. Hypersensitivity and anaphylaxis
2. Myocarditis and pericarditis
3. Anxiety-related reaction
4. Concurrent illness
5. Thrombocytopenia and coagulation disorder
6. Immunocompromised individuals

Serial measurement of anti-spike immunoglobulin M (IgM)/immunoglobulin G (IgG)/total antibody and surrogate neutralising antibody.

Measurement of the immunity after vaccination among the Healthcare worker through laboratory testing. The exclusion criteria were experienced with PCR –confirmed COVID-19 or positive test for severe acute respiratory syndrome coronavirus 2–specific IgG or IgM in the serum

Positive anti-spike IgG in Pfizer higer than Sinovac by 3 methods and majority developed anti-spike IgG after dose 2 with no significant difference between Pfizer and Sinovac. Abbott assay showed that the antibody levels of people who received two doses of Pfizer were approximately 11 times higher than that of Sinovac.

To determine vaccine-induced NAb escape by B.1.617.2 and compare activity to previous strains

Prospective cohort study in vaccinated employee of either UCLH (University College London Hospital) or The Francis Crick Institude measuring neutralising antibody titres against Wild type strain and variants

• Neutralising antibody titres after two doses of BNT162b2 (Pfizer) were 5.8-fold reduced against B.1.617.2 and 4.9 -fold reduced against B.1.351 relative to Wild-type.
• After one dose of BNT162b2 (Pfizer), 75% of samples had low neutralising antibody titres against B.1.351 and 68% of samples had low neutralising antibody titres against B.1.617.2.
• Increased age and time after the second dose of BNT162b2 (Pfizer) correlated with reduced neutralising antibody titres.
  

• Most participants that recieved two doses of BNT162b2 (Pfizer) would be protected against B.1.617.2 infection.
• Single-dose recipients are likely to be less protected against these SARS-CoV-2 variants.
• Both increased age and time since the second dose of BNT162b2 (Pfizer) significantly correlate with decreased neutralising antibody activity against B.1.617.2 and B.1.351.

To measure the resistance of wild-type, the D614G mutation, and the B.1.1.7 and B.1.351 variants to neutralization elicited by infection or vaccination

Evaluation of pseudovirus resistance to neutralization using convalescent serum obtained from 34 patients 5 months after infection with Covid-19 and serum from 50 participants obtained 2 to 3 weeks after receipt of the second dose of Sinopharm or Sinovac

• Neutralization against the wild-type:
  
  • Similarly in convalescent serum and vaccinees’ serum, suggested a low antibody response after two-dose inoculation induced by Sinopharm and Sinovac.
    
• Neutralization against variants:
  
  • The convalescent serum was significantly more effective in alpha variant than beta variant. 9 of 30 convalescent serum samples showed complete loss of neutralizing activity against beta variants
    
  • In Sinopharm serum: similar to wild-type virus (low antibody response), and 20 serum samples showed complete or partial loss of neutralization against the beta variant.
    
  • In Sinovac serum: marked decrease antibody response against alpha and beta variants compared to wild-type, and most of the serum samples showed complete or partial loss of neutralization against beta variants

Our findings suggest that alpha variants showed less resistance to the neutralizing activity of convalescent or vaccinee serum, compared to the beta variants.

To enhance public confidence in vaccines and accelerate their uptake process

A cross-sectional study for the side effects (SE) of CoronaVac among Turkish healthcare workers who received either one or two doses of the CoronaVac vaccine during the last 30 days by using questionnaire inquired about local and systemic SEs and statistical tests were carried out by SPSS

• Turkish healthcare worker experienced
  
  • Most common local side effect: injection site pain (41.5%)
    
  • The common systemic side effects: fatigue (23.6%), headache (18.7%), muscle pain (11.2%) and joint pain (5.9%)
• Female healthcare workers were significantly more affected. Younger age, previous infection, and chronic illnesses and regular medicines uptake can be associated with an increased risk of CoronaVac side effects

• Higher prevalence of CoronaVac SEs than what is reported by phase I–III clinical trials.
• In general, the results of this study confirm the overall safety of CoronaVac and suggest potential risk factors for its SEs.
• Gender-based differences and SEs distribution among age groups are worth further investigation

To evaluate the safety and efficacy of a single dose of Ad26.COV2.S (Janssen) at 5×10¹⁰ viral particles for the prevention of Covid-19 and SARS-CoV-2 infection in adults.

• Phase 3 multicenter randomized controlled trials
• 43783 Adults were randomly assigned in 1:1 ratio to receive vaccine or placebo
• Analyzed the efficacy against Covid-19 at least 14 and 28 days after vaccinated

• Vaccine efficacy was higher against severe–critical Covid-19 (76.7% [adjusted 95% CI, 54.6 to 89.1] for onset at ≥14 days and 85.4% [adjusted 95% CI, 54.2 to 96.9] for onset at ≥28 days)
• The incidence of serious adverse events was balanced between the two groups.

A single dose of Ad26.COV2.S (Janssen) protected against symptomatic Covid-19 and asymptomatic SARS-CoV-2 infection and was effective against severe–critical disease, including hospitalization and death. Safety appeared to be similar to that in other phase 3 trials of Covid-19 vaccines.

Remarks:

Lower vaccine efficacy has been associated with a higher incidence of disease. This situation, combined with the emergence of viral variants, precludes the comparison of vaccine trials

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Indications

Active immunization to prevent COVID-19 caused by SARS-CoV-2 virus in individuals from 18 to 59 years of age

Dose

2 Dose

Interval

14 – 28 days

Contraindication

1. People with history of severe allergic reaction to CoronaVac or other inactivated vaccines (e.g., acute anaphylaxis, angioedema, dyspnea, etc.)