Differences in IgG Antibody Responses following BNT162b2 and mRNA-1273 SARS-CoV-2 Vaccines

ABSTRACT Studies examining antibody responses by vaccine brand are lacking and may be informative for optimizing vaccine selection, dosage, and regimens. The purpose of this study is to assess IgG antibody responses following immunization with BNT162b2 (30 μg mRNA) and mRNA-1273 (100 μg mRNA) vaccines. A cohort of clinicians at a nonprofit organization is being assessed clinically and serologically following immunization with BNT162b2 or mRNA-1273. IgG responses were measured at the Remington Laboratory by an IgG assay against the SARS-CoV-2 spike protein-receptor binding domain. Mixed-effect linear (MEL) regression modeling was used to examine whether the SARS-CoV-2 IgG level differed by vaccine brand, dosage, or number of days since vaccination. Among 532 SARS-CoV-2 seronegative participants, 530 (99.6%) seroconverted with either vaccine. After adjustments for age and gender, MEL regression modeling revealed that the average IgG antibody level increased after the second dose compared to the first dose (P < 0.001). Overall, titers peaked at week 6 for both vaccines. Titers were significantly higher for the mRNA-1273 vaccine on days 14 to 20 (P < 0.05), 42 to 48 (P < 0.01), 70 to 76 (P < 0.05), and 77 to 83 (P < 0.05) and higher for the BNT162b2 vaccine on days 28 to 34 (P < 0.001). In two participants taking immunosuppressive drugs, the SARS-CoV-2 IgG antibody response remained negative. mRNA-1273 elicited higher IgG antibody responses than BNT162b2, possibly due to the higher S-protein delivery. Prospective clinical and serological follow-up of defined cohorts such as this may prove useful in determining antibody protection and whether differences in antibody kinetics between the vaccines have manufacturing relevance and clinical significance. IMPORTANCE SARS-CoV-2 vaccines using the mRNA platform have become one of the most powerful tools to overcome the COVID-19 pandemic. mRNA vaccines enable human cells to produce and present the virus spike protein to their immune system, leading to protection from severe illness. Two mRNA vaccines have been widely implemented, mRNA-1273 (Moderna) and BNT162b2 (Pfizer/BioNTech). We found that, following the second dose, spike protein antibodies were higher with mRNA-1273 than with BNT162b2. This is biologically plausible, since mRNA-1273 delivers a larger amount of mRNA (100 μg mRNA) than BNT162b2 (30 μg mRNA), which is translated into spike protein. This difference may need to be urgently translated into changes in the manufacturing process and dose regimens of these vaccines.

2) Did the authors assess for COVID infection of participants throughout the duration of they study, or just prior to vaccination? Was it possible infection during the study impacted observed antibody titers?
3) Line 48. The authors state that "mRNA-1273 elicited both earlier and higher IgG antibody responses . . ." The authors did demonstrate statistically that higher overall Aby response was observed with 1273; however the data doesn't support that statistically 1273 had earlier response (only 2 subjects were positive and not statistically different). This statement should be modified. 4) Line 62. Please clarify that the vaccine doesn't deliver a higher amount of spike protein. It delivers a higher level of mRNA that is translated into spike protein. Please clarify other instances similar to this throughout the manuscript. 5) Line 97. Please add reference for Remington Lab data or state data no shown. 6)Line 191. Did the authors evaluate T-cell immunity in this cohort? If so, that would be valuable data to include. Minimally, this should be indicated as "data not shown".
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Thank you for submitting your paper to Microbiology Spectrum. Below please find our point-by-point responses to the issues raised by the reviewers In an attempt to more clearly present our answers to each comment, we have repeated here each comment and kept the same order in which they appeared in the e-mail sent to us by Microbiology Spectrum.
In the revised manuscript we have underlined the text that has been modified or added.
Reviewer #1 (Comments for the Author): The manuscript by Montoya et al has assessed IgG antibody titers in a cohort of health care workers vaccinated with 1 of 2 mRNA vaccines. In this initial phase of their study, they present results 3 months post vaccination and conclude that statistically higher immune response is observed for the mRNA-1273 vaccine. The authors have addressed prior reviewer comments and updated the manuscript accordingly.

Answer: Thank you. As you know our study addressed the immune responses to
BNT162b2 and mRNA-1273 Vaccines and as you point, there was statistically higher immune response with the mRNA-1273 vaccine.

Major comments:
Page 2 of 4 1) This is the initial phase of a planned > 1 year study. The conclusions from the study would have higher impact if the authors waited to have the full 1 yr data set, specifically in regards to the overall IgG decay in their cohort.
Answer: We agree with the reviewer that conclusions from our study will eventually have higher impact when our 1 year follow-up results become available. We still believe that there is merit in publishing our early results since they support the results of two other studies that were published despite that they are within the first 3 3) Line 48. The authors state that "mRNA-1273 elicited both earlier and higher IgG antibody responses . . ." The authors did demonstrate statistically that higher overall Aby response was observed with 1273; however the data doesn't support that statistically 1273 had earlier response (only 2 subjects were positive and not statistically different). This statement should be modified. 6) Line 191. Did the authors evaluate T-cell immunity in this cohort? If so, that would be valuable data to include. Minimally, this should be indicated as "data not shown".
Answer: Unfortunately, we did not evaluate T-cell mediated immunity. We have added this to our list of limitations (Line 186-188) Your manuscript has been accepted, and I am forwarding it to the ASM Journals Department for publication. You will be notified when your proofs are ready to be viewed.
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