Eleven-month SARS-CoV-2 binding antibody decay, and associated factors, among mRNA vaccinees: implications for booster vaccination
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Background. We examined the 11 month longitudinal antibody decay among two-dose mRNA vaccinees, and identified factors associated with faster decay.
Methods. The study included samples from the COVID-19 Occupational Risk, Seroprevalence and Immunity among Paramedics (CORSIP) longitudinal observational study of paramedics in Canada. Participants were included if they had received two mRNA vaccines without prior SARS-CoV-2 infection and provided two blood samples post-vaccination. The outcomes of interest were quantitative SARS-CoV-2 antibody concentrations. We employed spaghetti and scatter plots (with kernel-weighted local polynomial smoothing curve) to describe the trend of the antibody decay over 11 months post-vaccine and fit a mixed effect exponential decay model to examine the loss of immunogenicity and factors associated with antibody waning over time.
Results. This analysis included 652 blood samples from 326 adult paramedics. Total anti-spike antibody levels peaked on the twenty-first day (antibody level 9042 U ml −1 ) after the second mRNA vaccine dose. Total anti-spike antibody levels declined thereafter, with a half-life of 94 [95 % CI: 70, 143] days, with levels plateauing at 295 days (antibody level 1021 U ml −1 ). Older age, vaccine dosing interval <35 days, and the BNT162b2 vaccine (compared to mRNA-1273 vaccine) were associated with faster antibody decay.
Conclusion. Antibody levels declined after the initial mRNA series with a half-life of 94 days, plateauing at 295 days. These findings may inform the timing of booster vaccine doses and identifying individuals with faster antibody decay.
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The work presented is clear and the arguments well formed. This is a study that would be of interest to the field and community.
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The authors have addressed the comments raised and I am happy with their response. I recommend that this important be accepted and published.
Please rate the manuscript for methodological rigour
Very 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 the manuscript involved human and/or animal experimentation, have the subjects been treated in an ethical manner and has …
Comments to Author
The authors have addressed the comments raised and I am happy with their response. I recommend that this important be accepted and published.
Please rate the manuscript for methodological rigour
Very 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 the manuscript involved human and/or animal experimentation, have the subjects been treated in an ethical manner and has ethical permission been provided?
Yes: Ethical approval was provided for the work
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This is a study that would be of interest to the field and community. The reviewers have highlighted minor concerns with the work presented. Please ensure that you address their comments.
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Comments to Author
REVIEWERS REPORT 11-month SARS-CoV-2 immunogenicity decay, and associated factors, among mRNA vaccinees: Implications for Booster Vaccination General comment In the paper '11-month SARS-CoV-2 immunogenicity decay, and associated factors, among mRNA vaccinees: Implications for Booster Vaccination', Asamoah-Boaheng et al, described the decay profile of binding antibody responses from participants that have received two doses of mRNA vaccines (BNT162b2 and mRNA-1273). They showed that the binding antibody responses peaked at about 21 days post-vaccination and plateaus at about ten months with a half-life of 94 days. They also showed that several factors, such as older age, vaccine type and timing of booster dosage, were associated with the decay rate of antibody immune responses. The background knowledge …
Comments to Author
REVIEWERS REPORT 11-month SARS-CoV-2 immunogenicity decay, and associated factors, among mRNA vaccinees: Implications for Booster Vaccination General comment In the paper '11-month SARS-CoV-2 immunogenicity decay, and associated factors, among mRNA vaccinees: Implications for Booster Vaccination', Asamoah-Boaheng et al, described the decay profile of binding antibody responses from participants that have received two doses of mRNA vaccines (BNT162b2 and mRNA-1273). They showed that the binding antibody responses peaked at about 21 days post-vaccination and plateaus at about ten months with a half-life of 94 days. They also showed that several factors, such as older age, vaccine type and timing of booster dosage, were associated with the decay rate of antibody immune responses. The background knowledge is explicit, the methodology is rigorous, and the findings are clear. However, the article will benefit from minor revisions on the points noted below. The word immunogenicity in the title is broad; however, the study focuses on binding antibody responses. The author may need to include in the limitation why they didn't measure T cell response which is also covered under immunogenicity. They may change immunogenicity to binding antibody decay, which is what they did. Secondly, the methodology will be clearer if the authors indicate the timing of the blood sampling. Were both first and second blood samples collected at the same time for each participant? It was until Lines 130-132 that they talked about grouping the participants into quartiles that I inferred the samples were not collected at the same time. If the samples were not collected simultaneously, it might be better to delete the word serially in the discussion because the sample collection wasn't serial. Moreso, in the discussion, reference 26 Line 206 did not agree with the result of this work because the immunity declined within one month, while in this study, the immunity peaked at 21 days, almost one month. The author needs to clarify and provide a reason for the results' differences. Also, the reference for the study cited in lines 207-210 needed to be provided. Finally, for other minor comments, figure 2 is unclear whether the time point shown is for the first or second blood collection or both and similarly in Figure S1. Line 82, the 19 in COVID-19, is missing. The age range for the participants needs to be provided. Line 158 should read a mean age 'of' not 'was'.
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 the manuscript involved human and/or animal experimentation, have the subjects been treated in an ethical manner and has ethical permission been provided?
Yes: The ethical permission was provided for the study
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Comments to Author
11-month SARS-CoV-2 immunogenicity decay, and associated factors, among mRNA 2 vaccinees: Implications for Booster Vaccinatio Title needs work. I don't think its the "immunogenicity" which decays over that period; i think this is the incorrect terminology. Needs to be a bit snappier as well. Need to make sure that the raw data is made available as they discuss calculation of decay rates based on this. Otherwise this is a very high quality paper which i considered insightful and which I enjoyed reading. The only thing I think needs to be considered, is that there is a lack of discussion around "protective" levels of antibodies in this context, what is known and what is considered protective, and then how appropriate these arbitrary cut-offs are, given many people will retain significant protection …
Comments to Author
11-month SARS-CoV-2 immunogenicity decay, and associated factors, among mRNA 2 vaccinees: Implications for Booster Vaccinatio Title needs work. I don't think its the "immunogenicity" which decays over that period; i think this is the incorrect terminology. Needs to be a bit snappier as well. Need to make sure that the raw data is made available as they discuss calculation of decay rates based on this. Otherwise this is a very high quality paper which i considered insightful and which I enjoyed reading. The only thing I think needs to be considered, is that there is a lack of discussion around "protective" levels of antibodies in this context, what is known and what is considered protective, and then how appropriate these arbitrary cut-offs are, given many people will retain significant protection in the absence of detectable antibody response to many viruses, how much is this a consideration in this case, it should at least be considered in the discussion. I have minor suggestions asside from changes to the title Line 36: Define CORSIP Line 193: The vaccine is immunogenic, the participants are immunised. Should read "Long term protection afforded by immunisation of serially-tested middle-aged vaccinees with two doses of mRNA vaccine was investigated"
Please rate the manuscript for methodological rigour
Very 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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