mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

Abstract

To date severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has infected over 100 million individuals resulting in over two million deaths. Many vaccines are being deployed to prevent coronavirus disease 2019 (COVID-19) including two novel mRNA-based vaccines1,2. These vaccines elicit neutralizing antibodies and appear to be safe and effective, but the precise nature of the elicited antibodies is not known3–6. Here we report on the antibody and memory B cell responses in a cohort of 20 volunteers who received either the Moderna (mRNA-1273) or Pfizer-BioNTech (BNT162b2) vaccines. Consistent with prior reports, 8 weeks after the second vaccine injection volunteers showed high levels of IgM, and IgG anti-SARS-CoV-2 spike protein (S) and receptor binding domain (RBD) binding titers3,5,6. Moreover, the plasma neutralizing activity, and the relative numbers of RBD-specific memory B cells were equivalent to individuals who recovered from natural infection7,8. However, activity against SARS-CoV-2 variants encoding E484K or N501Y or the K417N:E484K:N501Y combination was reduced by a small but significant margin. Consistent with these findings, vaccine-elicited monoclonal antibodies (mAbs) potently neutralize SARS-CoV-2, targeting a number of different RBD epitopes in common with mAbs isolated from infected donors. Structural analyses of mAbs complexed with S trimer suggest that vaccine- and virus-encoded S adopts similar conformations to induce equivalent anti-RBD antibodies. However, neutralization by 14 of the 17 most potent mAbs tested was reduced or abolished by either K417N, or E484K, or N501Y mutations. Notably, the same mutations were selected when recombinant vesicular stomatitis virus (rVSV)/SARS-CoV-2 S was cultured in the presence of the vaccine elicited mAbs. Taken together the results suggest that the monoclonal antibodies in clinical use should be tested against newly arising variants, and that mRNA vaccines may need to be updated periodically to avoid potential loss of clinical efficacy.

Longitudinal analysis of humoral immunity against SARS-CoV-2 Spike in convalescent individuals up to 8 months post-symptom onset

“…A recent study comparing humoral immunity generated by mRNA vaccinees (mRNA-1273 or BNT162b2) and individuals recovered from natural infection observed similarities in antibody binding titers and plasma neutralization capacity (36). Furthermore, this study also observed similar frequencies of RBD-specific memory B cells between vaccinees and infected individuals.…”

Molecular Epidemiology Surveillance of SARS-CoV-2: Mutations and Genetic Diversity One Year after Emerging

“…Recent reports have shown that mutations in the S protein are becoming more frequent as the pandemic spreads and that these mutations can have an increased capacity to spread [51,52]. To date, most serum samples from either volunteers in vaccines trials or patients recovering from COVID-19 have shown full or slightly diminished capacity to inactivate some of the more widespread SARS-CoV-2 variants, except for B.1.1.7 (N501Y substitution), 501Y.V2 (N501Y, K417N and E484K substitutions) and 501.V3 (N501Y and E484K substitutions), which have been able to cause a decrease in the neutralization assays using the aforementioned serum samples [53][54][55][56].…”

Sequence signatures of two IGHV3-53/3-66 public clonotypes to SARS-CoV-2 receptor binding domain

“…In particular, a lot of attention has been focused on RBD mutation E484K, which has emerged in multiple independently SARS-CoV-2 lineages 63, 64 and can alter the antigenicity of the spike protein [65][66][67] . Another naturally occurring RBD mutation, K417N, which has emerged in South Africa and Brazil (B.1.351 lineage and B.1.1.28, respectively) 63, 64,68 , has recently been shown to also alter antigenicity of the spike protein 66,[69][70][71] . Consistently, we found that K417N dramatically decreased the binding of COV107-23 (clonotype 1) and COVD21-C8 (clonotype 2)…”