Variant constraint by mRNA vaccines

Abstract

The currently licensed mRNA vaccines for SARS-CoV-2 can elicit cross-neutralizing antibodies against B.1.351 variants of the virus, but are less potent against these variants.

Several vaccines against SARS-CoV-2 are now licensed for use, but there is concern that they may be less effective against emerging variants of the virus. Stamatatos et al. now report that the mRNA vaccines designed against earlier variants of SARS-CoV-2 also elicit and boost levels of cross-neutralizing antibodies (nAbs) to newer B.1.351 variants, but are less potent against these variants.

The two mRNA vaccines that have received emergency use authorizations — BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna) — encode a stabilized ectodomain version of the spike (S) protein from the Wuhan-Hu-1 variant of SARS-CoV-2 (isolated in 2019). These vaccines elicit nAbs to the virus and show more than 94% efficacy in preventing disease. However, emerging variants of SARS-CoV-2 contain S protein mutations that could potentially evade the nAb responses induced by the vaccines. Of particular concern are variants that have emerged in the United Kingdom (B.1.1.7), South Africa (B.1.351) and Brazil (P.1) as they have mutations that may enhance transmissibility and disease severity, as well as vaccine evasion.

S. Bradbrook/Springer Nature Limited

The authors collected sera from 15 individuals who had previously been infected with SARS-CoV-2 and 13 individuals who had not been infected, both before and after immunization with one of the mRNA vaccines. They used pseudovirus systems to assess the ability of the sera to neutralize viruses expressing the Wuhan-Hu-1 S protein or two different versions of the B.1.351 S protein. Prior to vaccination, sera from 12 of the 15 previously infected donors (but not from any of the naive donors) neutralized the Wuhan-Hu-1 variant. By contrast, the sera from the unvaccinated previously infected donors showed weak and only sporadic neutralizing activity against the B.1.351 variants.

A single vaccine dose in previously infected individuals with pre-existing virus-specific antibodies induced higher levels of virus-specific IgG and IgA than two vaccine doses in naive individuals. A single vaccination in previously infected individuals also boosted nAb titres against all three of the SARS-CoV-2 variants tested. Again, this was to a greater extent than two vaccine doses in naive individuals, with the vaccinated previously infected individuals showing 10-fold and 20-fold higher levels of nAbs to the Wuhan-Hu-1 and B.1.351 variants, respectively. Antibody-depletion studies indicated that the majority of cross-neutralizing antibodies generated by the mRNA vaccines target the receptor-binding domain of the S protein. However, the serum of vaccinated previously infected individuals was 3- to 10-fold less efficient in neutralizing the B.1.351 variants than the Wuhan-Hu-1 variant.

the available mRNA vaccines for SARS-CoV-2 do induce cross-variant neutralizing antibodies

Overall, these results suggest that the available mRNA vaccines for SARS-CoV-2 do induce cross-variant neutralizing antibodies and highlight the importance of vaccinating previously infected as well as naive individuals to promote immunity to emerging variants. Another key finding was that a second dose of the vaccine within 3–4 weeks did not further boost nAb levels in the previously infected individuals, so second vaccine doses could be delayed in such cases.