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Review 2: "BNT162b2 vaccine boosts neutralizing antibodies to ancestral SARS-CoV-2 & Omicron variant in adults received 2-dose inactivated vaccine"

This study investigated the extent of the BNT162 third dose's protection in patients who received two doses of inactivated vaccines. The study found that the booster increased antibody levels against the ancestral strain and the Omicron VoC. Reviewers deem the claims reliable.

Published onFeb 13, 2022
Review 2: "BNT162b2 vaccine boosts neutralizing antibodies to ancestral SARS-CoV-2 & Omicron variant in adults received 2-dose inactivated vaccine"
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key-enterThis Pub is a Review of
BNT162b2 vaccine boosts neutralizing antibodies to ancestral SARS-CoV-2 & Omicron variant in adults received 2-dose inactivated vaccine

AbstractLimited data exist on antibody responses to mixed vaccination strategies involving inactivated COVID-19 vaccines, particularly in the context of emerging variants. We conducted an open label trial and administered a third vaccine dose of an mRNA vaccine (BNT162b2, BioNTech/Fosun Pharma) in adults aged ≥30 years who had previously received two doses of an inactivated COVID-19 vaccine. We collected blood samples prior to administering the third dose and 28 days later, and tested for antibodies to the ancestral virus using a binding assay (ELISA), a surrogate virus neutralization test (sVNT) and a live virus plaque reduction neutralization test (PRNT), and to the Omicron variant using PRNT. A third dose of BNT162b2 substantially increased antibody titers on each assay. Mean ELISA levels increased from an optical density (OD) of 0.3 to 2.1 (p<0.01), and mean sVNT levels increased from an inhibition of 17% to 96% (p<0.01). In a random subset of 20 participants, the geometric mean PRNT50 titers rose very substantially by at least 27 fold from Day 0 to Day 28 against the ancestral virus (p<0.01) and rose by at least 14 fold against the Omicron variant (p<0.01). In daily monitoring, post-vaccination reactions subsided within 7 days for over 99% of participants. In conclusion, a third dose of COVID-19 vaccination with an mRNA vaccine substantially improved antibody levels against the ancestral virus and against the Omicron variant with well-tolerated safety profile, in adults who had received two doses of inactivated vaccine 6 months earlier.

RR:C19 Evidence Scale rating by reviewers:

  • Strong. The main study claims are very well-justified by the data and analytic methods used. There is little room for doubt that the study produced has very similar results and conclusions as compared with the hypothetical ideal study. The study’s main claims should be considered conclusive and actionable without reservation.



Leung and colleagues report the outcome of booster mRNA vaccination in a population of 315 adults (75% above 47 years) that were immunized 6-7 months before with two doses of inactivated virus vaccine. Serum antibody neutralization increased by 27-fold and 14-fold when measured against wild-type virus and Omicron variant, respectively. Interestingly, levels of wt strain neutralizing antibodies were higher than previously reported for inactivated virus vaccine booster (21-fold increase). In this population, mRNA booster dose had an acceptable safety profile with fever and headache as the most commonly reported reactions. The study is thoughtfully executed and well described. Additionally, the report of booster vaccination in a population at risk of Covid-19 provides meaningful information on heterologous vaccination and the importance of third dose immunization to increase neutralization and putative protection against the Omicron variant.

Suggested changes:

1. Goldbatt and colleagues have recently reported the use of spike-specific IgG titer to determine vaccine protection, with a threshold of 60 antibody binding units (BAU) per mL ( for non-inferiority comparison of vaccines and estimation of protection against variants of concern. Therefore, authors should include Omicron-specific IgG titer and determine BAU/mL to corroborate the putative Omicron protection of mRNA booster dose discussed in lines 165-168.

2. Please clarify in text and figure S1 that participants included in the analysis did not report SARS-CoV-2 infection between vaccination and sampling to exclude that Omicron-specific neutralizing antibodies originated from natural infection due to the rapid diffusion of this variant in the study period.

3. Please add the statistical results described in the text in figure 1.

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