Researchers at NYU Grossman School of Medicine in New York have conducted a study demonstrating the effectiveness of the Pfizer-BioNtech BNT162b2 vaccine against recently emerged variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – the agent that causes coronavirus disease 2019 (COVID-19).
Nathaniel Landau and colleagues found that sera from vaccinated individuals neutralized recent variants more effectively than sera from convalescent individuals who had been infected before the variants emerged.
However, neutralizing antibody titers against the B.1.351 variant identified in South Africa were three times lower than those generated against an earlier variant – D614G – that became dominant in 2020.
The authors say this reduction in antibody titer was attributable to a specific mutation in the viral spike protein – the structure SARS-CoV-2 uses to bind to and infect host cells.
The mutation – called E484K – lies in an amino acid motif that is a key epitope for the binding of neutralizing antibodies.
“These findings suggest that antibodies elicited by primary infection and by the BNT162b2 mRNA vaccine are likely to maintain protective efficacy against B.1.1.7 and most other variants but that the partial resistance of virus with the B.1.351 spike protein could render some individuals less well protected, supporting a rationale for the development of modified vaccines containing E484K,” writes the team.
A pre-print version of the research paper is available on the bioRxiv* server, while the article undergoes peer review.
Concerns that SARS-CoV-2 variants could avoid neutralization
The increasing emergence of SARS-CoV-2 variants with mutations in the spike protein has sparked concerns over whether antibodies elicited by previous infection or vaccination will still neutralize the virus effectively.
Since the first cases of SARS-CoV-2 were identified in Wuhan, China, in late 2019, the viral spike protein has rapidly acquired mutations that select for optimal interaction with the host cell receptor angiotensin-converting enzyme 2 (ACE2) and for escape from neutralizing antibodies.
A variant with a D614G spike mutation identified in January 2020 quickly became the dominant strain, with a worldwide prevalence of more than 97% by May.
The B.1.1.7 variant that emerged in the UK in September 2020 has been found to contain 8 mutations in the spike protein, one of which (N501Y) has been shown to increase affinity for ACE2.
The B.1.351 variant identified in South Africa in October 2020 contains 9 mutations, of which three (K417N, E484K and N501Y) are located in the spike protein’s receptor-binding domain.
Other variants include the 20A.EU2 isolate identified in Spain and elsewhere in Europe, the COH.20G/677H lineage identified in Columbus, Ohio, and variants identified among domesticated minks in Denmark (with the potential to transfer to humans).
“Immunoevasion would have the potential to allow for the re-infection of individuals who have cleared the virus and could reduce the level of protection provided by currently approved vaccines and those in clinical trials which are based on the earlier viral isolate sequence,” says Landau and the team.
Examples of these vaccines include the Pfizer-BioNTech BNT162b2 and Moderna mRNA-1273 vaccines that have received emergency use authorization in several countries and are currently being rolled out as part of mass immunization efforts.
What did the researchers do?
Landau and colleagues investigated neutralizing activity against each of the variants using sera from convalescent individuals who had been infected before the variants emerged and sera from recipients of the Pfizer-BioNTech BNT162b2 vaccine.
Sera from the convalescent individuals neutralized B.1.1.7 (UK), B.1.351 (South Africa), 20A.EU2 (Europe) COH.20G/677H (Columbia), and mink (Denmark) variants with antibody titers similar to those generated against the earlier D614G variant.
Sera from individuals immunized with the Pfizer-BioNTech vaccine neutralized the D614G virus with antibody titers that were, on average, seven times higher than those observed for convalescent sera.
Vaccine-elicited antibodies neutralized the B.1.1.7 variant with titers similar to those seen with the D614G variant. They also neutralized B.1.351, although titers were three times lower than those generated against D614G.
The researchers say this reduced neutralizing antibody titer was attributable to the E484K mutation.
However, even with this 3-fold reduction, neutralizing antibody titers were still higher than those observed when convalescent sera neutralized D614G, they add.
What did the authors conclude?
Landau and colleagues say that overall, the findings suggest that the protection provided by vaccination will remain largely intact against the South African variant and other currently circulating variants.
However, “the partial resistance of B.1.351 to vaccine-elicited antibody could result in a reduced level of protection in individuals with a below average neutralizing titer,” they write.
“It will be important to define correlates of protection to understand the titer of neutralizing antibody required to provide protection against infection and disease pathogenesis and there is a need to produce modified vaccines based on variant mutations,” concludes the team.
bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.