Immunogenicity of bivalent versus monovalent mRNA booster vaccination among adult paramedics in Canada who had received three prior mRNA wild-type doses
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Introduction Comparative immunogenicity from different mRNA booster vaccines (directed at wild-type [WT], BA.1, or BA.4/5 antigens) remains unclear. Methods We included blood samples from adult paramedics who received three mRNA WT-directed vaccines plus a fourth dose of: (1) WT monovalent; (2) Moderna BA.1-WT bivalent; or (3) Pfizer BA.4/5-WT bivalent vaccine. The primary outcome was angiotensin-converting enzyme 2 (ACE-2) inhibition to BA.4/5 antigen. We used optimal pair matching (using age, sex-at-birth, preceding SARS-CoV-2 infection, and fourth vaccine-to-blood collection interval) to create balanced groups to individually compare each vaccine type to each other vaccine (overall, within subgroups defined by SARS-CoV-2 infection, and after combining BA.1 and BA.4/5 cases). We compared outcomes with Wilcoxon matched pairs signed rank test. Results Overall, 158 paramedics (mean age 45 years) were included. ACE-2 inhibition was higher for BA.1 compared to WT (p=0.002); however, no difference was detected between BA.4/5 vs. WT, or BA.1 vs BA.4/5. Among cases with preceding SARS-CoV-2, there were no between-group differences. Among cases without preceding SARS-CoV-2, the only difference was BA.1 > WT (p=0.003). BA.1 and BA.4/5 cases combined had higher ACE2 inhibition than WT (p = 0.003). Conclusion Omicron-directed vaccines appear to improve Omicron-specific immunogenicity; however, this appears limited to SARS-CoV-2-naïve individuals.
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I am pleased to tell you that your article has now been accepted for publication in Access Microbiology. I commend the authors on their articulate and measured response to reviewers. The authors have done an excellent job of revising their manuscript in line with reviewer comments.
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The reviewers have highlighted minor concerns with the work presented. Please ensure that you address their comments.
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Comments to Author
The authors describe a study to determine the effectiveness of a fourth dose of either a monovalent wild type vaccine or commercial bivalent vaccines in 158 paramedics in Canada. Some of these paramedics has prior exposure to SARS CoV-2 and some did not have evidence of prior infection. Each one of these paramedics had received three previous doses of the monovalent WT vaccine. The objective was to determine if Omicron directed commercial vaccines improve the Omicron specific immunogenicity. Overall, the result indicate that the Moderna bivalent vaccine is more effective than the Pfizer bivalent vaccine in inducing a higher response to the Omicron variant B.4/5. However, both vaccines do elicit some increased response, but this seems to be limited to the SARS CoV-2 naive individuals. Methodology …
Comments to Author
The authors describe a study to determine the effectiveness of a fourth dose of either a monovalent wild type vaccine or commercial bivalent vaccines in 158 paramedics in Canada. Some of these paramedics has prior exposure to SARS CoV-2 and some did not have evidence of prior infection. Each one of these paramedics had received three previous doses of the monovalent WT vaccine. The objective was to determine if Omicron directed commercial vaccines improve the Omicron specific immunogenicity. Overall, the result indicate that the Moderna bivalent vaccine is more effective than the Pfizer bivalent vaccine in inducing a higher response to the Omicron variant B.4/5. However, both vaccines do elicit some increased response, but this seems to be limited to the SARS CoV-2 naive individuals. Methodology seems to be rigorously determined as to study subjects and statistics. There are some limitations on number of naive individuals being smaller than those with prior SARS Cov-2 exposure. Results are presented as a narrative with data Tables being supplementary, Authors perhaps these tables should be included in the paper to support the narrative. It would be helpful on the Figures if you would explain the significant result or at least better identify the significant result, it is not clear from your legend. Also, not sure what the numbers in parentheses in Table 1 and supplementary Tables 1 and 2 represent? You have SD in your figure legend but not sure where the SD is mentioned in the Tables? Is this the number in parentheses? Please clarify. Also does the bar in the figures represent the average of the results? Style and presentation of the paper is acceptable but above questions should be considered with the objective of clarifying the results. The literature is brief but appropriate. The one limitation of the study is that you cannot make inferences to the general population. Your study group is a very narrow set of individuals that had previous multiple vaccinations with the monovalent WT SARS CoV-2, this seems a very different vaccinated group compared to the general population. Perhaps you can infer some information as to the value of multiple vaccinations? Are this many vaccinations warranted, and does it provide better protection? Does protection from four vaccinations last longer that those that receive the one bivalent commercial vaccine? If you can infer some reference to the value of multiple exposures to the vaccines, please do so. Definitely an interesting and different paper considering the study group.
Please rate the manuscript for methodological rigour
Good
Please rate the quality of the presentation and structure of the manuscript
Good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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Comments to Author
This study has observed that Omicron-specific bivalent vaccine boosters could induce a higher humoral immune response against Omicron BA.4/5 subvariant than WT monovalent vaccine in paramedics without previous SARS-CoV-2 infections. While the manuscript is interesting, some concerns should be addressed. 1. In table 1, pre-Omicron infection was defined as SARS-CoV-2 infections that occur before November 26, 2021; and Omicron infections were defined as infections that occurred after December 26, 2021. How does this rough definition impact the conclusion, since the sample size is smaller? And to what extent? 2. In p8 line 157, there is a difference between groups, but not significant. The result description "not detect a difference" should be changed. The same description should be modified in lines 162 …
Comments to Author
This study has observed that Omicron-specific bivalent vaccine boosters could induce a higher humoral immune response against Omicron BA.4/5 subvariant than WT monovalent vaccine in paramedics without previous SARS-CoV-2 infections. While the manuscript is interesting, some concerns should be addressed. 1. In table 1, pre-Omicron infection was defined as SARS-CoV-2 infections that occur before November 26, 2021; and Omicron infections were defined as infections that occurred after December 26, 2021. How does this rough definition impact the conclusion, since the sample size is smaller? And to what extent? 2. In p8 line 157, there is a difference between groups, but not significant. The result description "not detect a difference" should be changed. The same description should be modified in lines 162 and167. Also please check other places carefully through the manuscript. 3. "ACE-2" should be unified to "ACE2" in the manuscript.
Please rate the manuscript for methodological rigour
Good
Please rate the quality of the presentation and structure of the manuscript
Satisfactory
To what extent are the conclusions supported by the data?
Partially support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
-
Comments to Author
The study is well performed, however it does not add any truly novel or groundbreaking insights for the field. It may be more rigorously discussed that we have to acknowlegde that the mRNA vaccines remain behind the expectations many people had to them, especially at this stage of the SARS.CoV-2 epidemics. Morover, side effects and PostVac effects need to be discussed.
Please rate the manuscript for methodological rigour
Good
Please rate the quality of the presentation and structure of the manuscript
Very good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential …
Comments to Author
The study is well performed, however it does not add any truly novel or groundbreaking insights for the field. It may be more rigorously discussed that we have to acknowlegde that the mRNA vaccines remain behind the expectations many people had to them, especially at this stage of the SARS.CoV-2 epidemics. Morover, side effects and PostVac effects need to be discussed.
Please rate the manuscript for methodological rigour
Good
Please rate the quality of the presentation and structure of the manuscript
Very good
To what extent are the conclusions supported by the data?
Strongly support
Do you have any concerns of possible image manipulation, plagiarism or any other unethical practices?
No
Is there a potential financial or other conflict of interest between yourself and the author(s)?
No
If this manuscript involves human and/or animal work, have the subjects been treated in an ethical manner and the authors complied with the appropriate guidelines?
Yes
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