Comparison of antibody response durability of mRNA-1273, BNT162b2, and Ad26.COV2.S SARS-CoV-2 vaccines in healthcare workers.

OBJECTIVES: There are limited comparative immunologic durability data post COVID-19 vaccinations. METHODS: Approximately 8.4 months after primary COVID-19 vaccination, 647 healthcare workers completed surveys about COVID-19 vaccinations/infections and blood draws. The groups included participants vaccinated with mRNA-1273 (n = 387), BNT162b2 (n = 212), or Ad26.COV2.S (n = 10) vaccines; unvaccinated participants (n = 10); and participants who received a booster dose (n = 28). The primary outcome was immunoglobin anti-spike titer. Secondary/tertiary outcomes included neutralizing antibodies (enzyme-linked immunosorbent assay-based pseudoneutralization) and vaccine effectiveness (VE). Antibody levels were compared using analysis of variance and linear regression. RESULTS: Mean age was 49.7 and 75.3% of the participants were female. Baseline variables were balanced except for immunosuppression, previous COVID-19 infection, and post-primary vaccination time. Unadjusted median (interquartile range [IQR]) anti-spike titers (AU/ml) were 1539.5 (876.7-2626.7) for mRNA-1273, 751.2 (422.0-1381.5) for BNT162b2, 451.6 (103.0-2396.7) for Ad26.COV2.S, 113.4 (3.7-194.0) for unvaccinated participants, and 31898.8 (21347.1-45820.1) for participants administered with booster dose (mRNA-1273 vs BNT162b2, P <.001; mRNA-1273, BNT162b2, or boosted vs unvaccinated, P <.006; mRNA-1273, BNT162b2, Ad26.COV2.S, or unvaccinated vs boosted, P <.001). Unadjusted median (IQR) pseudoneutralization was as follows: 90.9% (80.1-95.0) for mRNA-1273, 77.2% (59.1-89.9) for BNT162b2, 57.9% (36.6-95.8) for Ad26.COV2.S, 40.1% (21.7-60.6) for unvaccinated, and 96.4% (96.1-96.6) for participants administered with booster dose (mRNA-1273 vs BNT162b2, P <.001; mRNA-1273, BNT162b2, or boosted vs unvaccinated, P <.028; mRNA-1273, BNT162b2, Ad26.COV2.S, or unvaccinated vs boosted, P <.001). VE was 87-89% for participants administered mRNA-1273 vaccine, BNT162b2 vaccine, and booster dose, and 33% for Ad26.COV2.S (none significantly different). CONCLUSION: Antibody responses 8.4 months after primary vaccination were significantly higher with mRNA-1273 than those observed with BNT162b2.

Harmonization of Multiple SARS-CoV-2 Reference Materials Using the WHO IS (NIBSC 20/136): Results and Implications.

Background: There is an urgent need for harmonization between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology platforms and assays prior to defining appropriate correlates of protection and as well inform the development of new rapid diagnostic tests that can be used for serosurveillance as new variants of concern (VOC) emerge. We compared multiple SARS-CoV-2 serology reference materials to the WHO International Standard (WHO IS) to determine their utility as secondary standards, using an international network of laboratories with high-throughput quantitative serology assays. This enabled the comparison of quantitative results between multiple serology platforms. Methods: Between April and December 2020, 13 well-characterized and validated SARS-CoV-2 serology reference materials were recruited from six different providers to qualify as secondary standards to the WHO IS. All the samples were tested in parallel with the National Institute for Biological Standards and Control (NIBSC) 20/136 and parallel-line assays were used to calculate the relevant potency and binding antibody units. Results: All the samples saw varying levels of concordance between diagnostic methods at specific antigen-antibody combinations. Seven of the 12 candidate materials had high concordance for the spike-immunoglobulin G (IgG) analyte [percent coefficient of variation (%CV) between 5 and 44%]. Conclusion: Despite some concordance between laboratories, qualification of secondary materials to the WHO IS using arbitrary international units or binding antibody units per milliliter (BAU/ml) does not provide any benefit to the reference materials overall, due to the lack of consistent agreeable international unit (IU) or BAU/ml conversions between laboratories. Secondary standards should be qualified to well-characterized reference materials, such as the WHO IS, using serology assays that are similar to the ones used for the original characterization of the WHO IS.