The relationship between the number of COVID-19 vaccines and infection with Omicron ACE2 inhibition at 18-months post initial vaccination in an adult cohort of Canadian paramedics
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The coronavirus disease 2019 (COVID-19) pandemic, caused by the SARS-CoV-2 virus, has rapidly evolved since late 2019, due to highly transmissible Omicron variants. While most Canadian paramedics have received COVID-19 vaccination, the optimal ongoing vaccination strategy is unclear. We investigated neutralizing antibody (NtAb) response against wild-type (WT) Wuhan Hu-1 and Omicron BA.4/5 lineages based on the number of doses and past SARS-CoV-2 infection, at 18 months post initial vaccination (with a Wuhan Hu-1 platform mRNA vaccine [BNT162b2 or mRNA-1273}). Demographic information, previous COVID-19 vaccination, infection history, and blood samples were collected from paramedics 18 months post initial mRNA COVID-19 vaccine dose. Outcome measures were ACE2 percent inhibition against Omicron BA.4/5 and WT antigens. We compared outcomes based on number of vaccine doses (two vs. three) and previous SARS-CoV-2 infection status, using the Mann-Whitney U test. Of 657 participants, the median age was 40 years (IQR 33-50) and 251 (42%) were females. Overall, median percent inhibition to BA.4/5 and WT was 71.61% (IQR 39.44-92.82) and 98.60% (IQR 83.07-99.73), respectively. Those with a past SARS-CoV-2 infection had a higher median percent inhibition to BA.4/5 and WT, when compared to uninfected individuals overall and when stratified by two or three vaccine doses. When comparing two vs. three WT vaccine doses among SARS-CoV-2 negative participants, we did not detect a difference in BA.4/5 percent inhibition, but there was a difference in WT percent inhibition. Among those with previous SARS-CoV-2 infection(s), when comparing two vs. three WT vaccine doses, there was no observed difference between groups. These findings demonstrate that additional Wuhan Hu-1 platform mRNA vaccines did not improve NtAb response to BA.4/5, but prior SARS-CoV-2 infection enhances NtAb response.
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Thank you for submitting this revised manuscript to Access Microbiology and addressing the reviewer concerns. I am pleased to inform you know that it has now been accepted for publication. Congratulations to all authors!
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Thank you for submitting your manuscript to Access Microbiology. It has now been reviewed by two experts in the field and their comments are attached below. The reviewers have important concerns regarding the sample and the methodology, which need to be addressed and/or explained further. Additionally, Reviewer 2 suggests that a different order and a clearer presentation of the results, in particular those related to Fig. 3, would be beneficial for the readability of the manuscript. Please discuss the results presented in the manuscript in a broader, updated context regarding newer viral variants and the validity of the ACE2 assay. As per the nature of this platform, novelty is not essential for manuscript consideration and assessment.
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Comments to Author
1. Methodological rigour, reproducibility and availability of underlying data Did the authors adjust the neutralizing Ab titer considering comorbidities and previous infection while comparing two or three doses of vaccination? were the neutralizing Abs potency assessed by cVNT test? if yes, provide the result, if not it should be discussed as a limitation of the study. 2. Presentation of results The results must be presented in a better order and clear to the readers especially those related to Fig.3. 3. How the style and organization of the paper communicates and represents key findings This is satisfying. 4. Literature analysis or discussion Can be improved if the authors consider other cVNT and neutralizing Abs response from different platforms including protein vaccines in the same 180 days …
Comments to Author
1. Methodological rigour, reproducibility and availability of underlying data Did the authors adjust the neutralizing Ab titer considering comorbidities and previous infection while comparing two or three doses of vaccination? were the neutralizing Abs potency assessed by cVNT test? if yes, provide the result, if not it should be discussed as a limitation of the study. 2. Presentation of results The results must be presented in a better order and clear to the readers especially those related to Fig.3. 3. How the style and organization of the paper communicates and represents key findings This is satisfying. 4. Literature analysis or discussion Can be improved if the authors consider other cVNT and neutralizing Abs response from different platforms including protein vaccines in the same 180 days follow-up (find at https://doi.org/10.1038/s41598-023-35147-y). 5. Any other relevant comments
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
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Comments to Author
This article focused on ACE2 percent inhibition against omicron BA4/5 and wilt-type Wuhan Hu-1 after two or three Wuhan Hu-1 platform mRNA vaccinations. The authors found that additional vaccines did not improve ACE2 inhibition to BA4/5, but post-infection. However, it is not clear where the novelty of this study lies, as many previous studies have demonstrated that multiple doses of vaccines corresponding to the origin strain do not increase neutralizing antibody activity against the Omicron strain. The sample size was not large, and the omicron strain was only BA4.5, so there was little information on other mutant strains (at least alpha, delta, BA1, or BA2 should be considered). The study population is also limited to paramedics (probably healthy young people). Furthermore, I think that there is a …
Comments to Author
This article focused on ACE2 percent inhibition against omicron BA4/5 and wilt-type Wuhan Hu-1 after two or three Wuhan Hu-1 platform mRNA vaccinations. The authors found that additional vaccines did not improve ACE2 inhibition to BA4/5, but post-infection. However, it is not clear where the novelty of this study lies, as many previous studies have demonstrated that multiple doses of vaccines corresponding to the origin strain do not increase neutralizing antibody activity against the Omicron strain. The sample size was not large, and the omicron strain was only BA4.5, so there was little information on other mutant strains (at least alpha, delta, BA1, or BA2 should be considered). The study population is also limited to paramedics (probably healthy young people). Furthermore, I think that there is a lack of data regarding judgments based solely on ACE2 percent inhibition rate as a surrogate marker, rather than on neutralizing antibodies or clinical efficacy. Data is lacking if the primary outcome is the ACE2 percent inhibition rate (for example, no vaccine, one dose, four doses, or subjects of various ages and backgrounds). I think that significant revisions are necessary for publication in a professional journal.
Please rate the manuscript for methodological rigour
Poor
Please rate the quality of the presentation and structure of the manuscript
Poor
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
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