mRNA Vaccines Against SARS-CoV-2 Differ in Antibody Response

The Pfizer-BioNTech and Moderna mRNA COVID-19 vaccines differ in the levels of antibody response they provoke, according to results from a head-to-head comparison and the analysis by age of the vaccine recipients.

Jeffrey Wilson, MD, PhD., Division of Allergy and Clinical Immunology, University of Virginia, Charlottesville, VA, and colleagues obtained quantitative assays for IgG to SARS-CoV-2 spike-receptor binding domain (RBD) and nucleocapsid after the 1st dose for some, and after the 2nd dose for all of the cohort of 167 vaccine recipients.

The investigators did not measure neutralizing antibodies (nAbs), which they acknowledge as a limitation in the study but note that others have established good correlation between the SARS-CoV-2 binding and neutralizing antibodies.

"One of the reasons we believe that studying binding antibodies (Abs) is important is that it is the only test that is readily available at low cost and can be implemented at scale," Wilson explained to Contagion. "This is not true for assays that measure nAbs or B or T cell memory."

Wilson commented on the purpose and limits of this study, characterizing it as "a small piece of a big puzzle."

"A comprehensive comparison of the two vaccines would require analysis of nAbs, B cell memory and T cells," Wilson said. "However there is already good data showing a strong correlation between binding Abs and nAbs and all of these immune metrics are indirect markers of the most important outcome, which is protection from infection and/or clinical disease."

The median age of the 167 vaccine recipients was 42 (interquartile range, 32-57 years), with 63 recipients (38%) aged 50 years or greater.There were no statistically significant differences between the vaccine groups in their numbers by age, sex or race.

The investigators found lower Abs levels in recipients of the mRNA vaccine from Pfizer-BioNTech than from Moderna; at both 14-28 days after the first dose, 5.9μg/ml (95% CI, 3.7-9.69μg/ml) vs 19.19μg/ml (15.8-23.19μg/ml), and 7-31 days after the 2nd dose, 45.9 μg/ml (37.0-57.0 μg/ml) vs 68.5 μg/ml (61.9-75.7).

Lower antibody levels after one or both injections were found with the Pfizer-BioNTech vaccine than with the Moderna vaccine in those 50 years of age or older; and these were lower than in younger recipients of the Pfizer-BioNTech vaccine. The levels achieved with the Moderna vaccine, however, were not statistically different between age groups. The investigators suggest that the apparent difference in immunogenicity observed in older adults might be attributed to the 30μg of mRNA contained in the Pfizer product vs 100 μg in the Moderna formulation.

"I think our study suggests that regulatory agencies should be taking a careful look at the data, looking specifically at outcomes in high-risk groups," Wilson said. "Although on aggregate both mRNA vaccines are performing well, it is possible that there are differences in certain populations that could warrant a recommendation. Of course, there is already precedent for this sort of thing in influenza, where the high dose FluZone is targeted to subjects 65 and over."

The investigators recommend additional studies to determine whether binding antibodies to SARS-CoV-2 can be used to predict clinical protection against COVID-19, and Wilson cautioned against expecting these to reveal a short-cut in vaccine development in the near-term.

"Until an immune correlate of protection is identified, I don't think there is a way around large population-based studies," Wilson said.