Elevated neutralizing antibody titers and SARS-CoV-2 variants

11/04/2021


There is growing concern that emerging variants of SARS-CoV-2 may evade neutralizing antibodies induced by prior
infection or vaccination, through mutations in the spike protein, including the receptor-binding domain (RBD). A
group of researchers from the Department of Microbiology at Mount Sinai Hospital School of Medicine, in New York
City, USA, note in the article "SARS-CoV-2 spike E484K mutation reduces antibody neutralization," that the
substitution of asparagine (N) by tyrosine (Y) at position 501 (N501Y), present in the variants belonging to the
B.1.1.7, B.1.351, and P.1 lineages, does not appear to affect the in vitro neutralization of convalescent or postvaccination human serum. Other substitutions, however, such as the E484K present in the B.1.351 and P.1 lineages,
could evade neutralizing antibodies.

This group of researchers has conducted several neutralization trials using convalescent serum with different levels of
SARS-CoV-2 antibody titers, and serum from individuals who received two doses of the Pfizer-BioNTech BNT162b2
COVID-19 vaccine. Their results suggest that a single mutation (E484K) present in the PANGO (Phylogenetic
Assignment of Named Global Outbreak) B.1.351 and B.1.1.28.1 lineages, alias SARS-CoV-2 P.1, could affect the
neutralizing activity of convalescent and post-vaccination polyclonal serum (infected with previous strains of SARSCoV-
2). However, they point out that serum containing high neutralizing antibody titers would still be able to
neutralize the E484K rSARS-CoV-2 mutation.

It is not yet clear which neutralizing antibody titer correlates with total protection, or the extent to which other
immune mechanisms, such as cell cytotoxicity dependent on non-neutralizing antibodies, or T-cell-mediated
immunity, contribute to protection. However, the results from this research group highlight the importance of
vaccines inducing high neutralizing antibody titers, in order to maximize protection against SARS-CoV-2 variants.
They also cite the need for the global vaccination effort to achieve the target of full vaccination in as many people as
possible.

Source: Sonia Jangra et al. SARS-CoV-2 spike E484K mutation reduces antibody neutralization. The Lancet. 7 April
2021.

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