Immunology: mRNA vaccines slightly less effective against some SARS-CoV-2 variants

The neutralizing activity of the Moderna and Pfizer-BioNTech mRNA vaccines against SARS-CoV-2 is reduced by a small margin against the variants N501Y (a mutation prevalent in the United Kingdom and South Africa), E484K and the combination K417N:E484K:N501Y. The findings, based on a study of 20 individuals, suggest that these vaccines may need to be updated periodically to avoid potential loss of clinical efficacy. The research is published online in Nature.

To investigate the response of antibodies and memory B cells — immune cells that remain in the body after infection and can rapidly proliferate and generate antibodies against SARS-CoV-2 upon reinfection — to mRNA vaccination, Michel Nussenzweig and colleagues collected blood samples from 20 individuals who had received two doses of either the Moderna mRNA-1273 vaccine (14 people) or the Pfizer-BioNTech BNT162b2 vaccine (6 people). The authors found that the vaccines led to the production of neutralizing antibodies, which targeted the same epitopes on the receptor binding domain of SARS-CoV-2 as those produced as a result of natural infection. They also observed that individuals immunized with either of the two vaccines produced closely related and nearly identical antibodies.

To determine whether blood plasma from the vaccinated individuals could neutralize circulating variants of SARS-CoV-2, the authors tested plasma samples against retroviruses that had been modified to express one of ten mutant forms of the SARS-CoV-2 spike protein. These included the receptor binding domain mutations N501Y, E484K and K417N, and a combination of all three. The authors found that there was a one- to three-fold decrease in neutralizing activity against the E484K, N501Y and K417N:E484K:N501Y variants. Fourteen of the 17 most potent monoclonal antibodies tested showed reduced neutralization of the N501Y, E484K and K417N variants.

Whether neutralizing antibodies against other epitopes not found in the receptor binding domain are elicited by these vaccines remains to be determined, the authors note. However, they conclude that the vaccines may need to be updated and immunity monitored in order to compensate for the evolution of the virus.