Ebony Hilton, MD, receives the first COVID-19 vaccine administered at UVA Health.
A study by researchers at the University of Virginia, Charlottesville, VA, USA, has shown why it is not only important to get vaccinated, but why it is just as important to get boosted and this is especially true for those vaccinated with Pfizer's BNT162b2 vaccine, but also for those vaccinated with either Moderna's mRNA-1273 vaccine or the single-shot Johnson & Johnson Ad26.COV2.S vaccine.
It shows that for the Pfizer vaccine, antibody levels rose more slowly than with the Moderna mRNA vaccine and fall more quickly, especially in older people. Antibody levels also fell with the Moderna vaccine, but age did not appear to make a significant difference. Peak levels were reached after about 20 days for all three vaccines, but levels for Pfizer and Moderna were some 50 times higher than with Johnson & Johnson's Ad26.COV2.S vaccine.
According to the University of Virginia news item:
Keshavarz and colleagues tracked post-vaccination antibody levels in 234 UVA employees over 10 months. In total, 114 had received Pfizer’s vaccine and 114 had received Moderna’s, while six had received Johnson & Johnson’s single shot.It is not surprising that antibody levels fall after vaccination, but we were struck by how rapidly the antibodies fell after the mRNA vaccines, particularly the Pfizer/BioNTech vaccine.
Dr Behnam Keshavarz PhD, lead author
Division of Allergy & Clinical Immunology, Department of Medicine University of Virginia, Charlottesville, VA, USA
A week to 20 days after their second dose, recipients of Pfizer’s and Moderna’s mRNA vaccines had antibody levels that were approximately 50 times higher those seen in the J&J recipients. Shortly thereafter antibodies from both Pfizer and Moderna began to drop, but the drop was more precipitous for Pfizer.
After six months, Pfizer vaccine recipients had antibody levels lower than both the Moderna recipients and patients who had been hospitalized with severe COVID-19 six months prior. (Patients who suffer severe COVID are thought to generate more antibodies than people who recover from mild cases.)Both Pfizer/BioNTech and Moderna have proven very effective in protecting against severe disease, but our study builds on others that have shown some subtle differences in outcomes that favor Moderna. This could particularly be true in higher risk populations, such as older subjects or those who have conditions with suppressed immune systems.
Dr Jeffrey Wilson, MD, PhD., senior author
Department of Pharmacology
University of Virginia, Charlottesville, VA, USA
The scientists note that while the Pfizer and Moderna vaccines are similar, there are differences in their formulations and the amount of mRNA they contain. This could explain the differences in antibody response they generate. Time between doses also could be a significant factor.
It’s important to understand that antibody levels are a relatively crude tool to assess vaccine effectiveness; doctors aren’t even sure there’s a direct correlation between antibody level and COVID-19 protection. Antibody levels naturally decline, whether after vaccination or illness, but the immune system remembers how to make the necessary antibodies when again confronted by the virus. Time has already told the most important story: All three vaccines examined in UVA’s study have performed remarkably well in protecting against severe illness, hospitalization and death.
IgG to SARS-CoV-2 spike RBD in an employee cohort. (A) Visualization of IgG levels with LOWESS curves in all samples collected from recipients of BNT162b2 (Pfizer/BioNTech), mRNA-1273 (Moderna) or Ad26.COV2.S (J&J/Janssen). The dashed line reflects the cut-off that was originally described for distinguishing positive and negative samples. (B) Comparison of levels at baseline, pre-boost (restricted to samples collected within one day of boost) and post-boost (7-31 days after the boost immunization) in recipients of BNT162b2 (P) or mRNA-1273 (M). Presented as GM with 95% CI and comparisons with Mann-Whitney U test. (C) Longitudinal data from subjects who had a sample at each of a baseline, pre-boost interval and post-boost interval, excluding subjects with prior COVID-19 infection (left). Level of pre-boost IgG as % in relation to post-boost IgG level, in subjects with longitudinal sampling (right).
Three COVID-19 vaccines have received FDA-authorization and are in use in the United States, but there is limited head-to-head data on the durability of the immune response elicited by these vaccines. Using a quantitative assay we studied binding IgG antibodies elicited by BNT162b2, mRNA-1273 or Ad26.COV2.S in an employee cohort over a span out to 10 months. Age and sex were explored as response modifiers. Of 234 subjects in the vaccine cohort, 114 received BNT162b2, 114 received mRNA-1273 and six received Ad26.COV2.S. IgG levels measured between seven to 20 days after the second vaccination were similar in recipients of BNT162b2 and mRNA-127 and were ~50-fold higher than in recipients of Ad26.COV2.S. However, by day 21 and at later time points IgG levels elicited by BNT162b2 were lower than mRNA-1273. Accordingly, the IgG decay curve was steeper for BNT162b2 than mRNA-1273. Age was a significant modifier of IgG levels in recipients of BNT162b2, but not mRNA-1273. After six months, IgG levels elicited by BNT162b2, but not mRNA-1273, were lower than IgG levels in patients who had been hospitalized with COVID-19 six months earlier. Similar findings were observed when comparing vaccine-elicited antibodies with steady-state IgG targeting seasonal human coronaviruses. Differential IgG decay could contribute to differences observed in clinical protection over time between BNT162b2 and mRNA-1273.It is clear from this study, that the vaccines alone, while they give good protection from the SARS-VoV-2 virus in the short term, the antibody levels they produce are not maintained in the long term. Nor are the antibody levels produced by infection, so boosters, and in all probability regular boosters are going to be needed until, if ever, the virus attenuates to become a mild infection which will maintain a good level of protection in the community by repeated re-infection.
Keshavarz, Behnam; Richards, Nathan E.; Workman, Lisa J.; Patel, Jaimin; Muehling, Lyndsey M.; Canderan, Glenda; Murphy, Deborah D.; Brovero, Savannah G.; Ailsworth, Samuel M.; Eschenbacher, Will H.; McGowan, Emily C.; Mann, Barbara J.; Nelson, Michael R.; Kadl, Alexandra; Woodfolk, Judith A.; Platts-Mills, Thomas A.E.; Wilson, Jeffrey M.
Trajectory of IgG to SARS-CoV-2 After Vaccination With BNT162b2 or mRNA-1273 in an Employee Cohort and Comparison With Natural Infection
Frontiers in Immunology 13; 2022; DOI: 10.3389/fimmu.2022.850987
Copyright: © 2022 The authors.
Open access
Reprinted under a Creative Commons Attribution 4.0 International license (CC BY 4.0)
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