The SARS-CoV-2 spike gene has accumulated mutations within the receptor-binding domain (RBD) and the N-terminal domain (NTD). These domains are major targets of the antibody response elicited by the vaccines. The RBD mutations include the N501Y mutation, which is associated with increased affinity of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) receptor. In contrast, the E484K and K417N RBD mutations and mutations in the NTD have been associated with neutralizing antibody escape. The B.1.1.7 (N501Y.V1) lineage, first identified in the United Kingdom, includes the N501Y mutation, which has been associated with 53% increased transmissibility. Neutralizing antibody activity elicited by infection or by mRNA vaccines against the B.1.1.7 variant are largely unaffected.
The B.1.351 (N501Y.V2) lineage first identified in South Africa contains the three RBD mutations and five additional NTD mutations. The sensitivity of B.1.351 to neutralizing antibodies from convalescent donors infected with the prototype lineage virus, assessed with a spike-pseudovirus neutralization assay, indicated that 48% of serum samples were unable to neutralize B.1.351, with the rest showing a reduction in neutralization titers by a factor of 3 to 86. This finding was corroborated by a live-virus neutralization assay, with reduction in antibody activity ranging from a factor of 6 to complete knockout for the B.1.351 variant. Another independent lineage of SARS-CoV-2 (P.1) also containing the E484K, K417N, and some B.1.351 NTD mutations has been identified in Brazil.
A pooled analysis of the efficacy of the ChAdOx1 nCoV-19 vaccine in the United Kingdom, Brazil, and South Africa, performed before the emergence of the B.1.351 and P.1 variants, reported an overall vaccine efficacy of 66.7% (95.8% confidence interval [CI], 57.4 to 74.0). Recent analysis of the efficacy of the ChAdOx1 nCoV-19 vaccine against the B.1.1.7 variant in the United Kingdom was 74.6% (95% CI, 41.6 to 88.9).
In this paper are reported findings from a multicenter phase 1b–2 trial in South Africa evaluating the safety, immunogenicity, and efficacy of the ChAdOx1 nCoV-19 vaccine in preventing symptomatic Covid-19. In the primary end-point analysis, mild-to-moderate Covid-19 developed in 23 of 717 placebo recipients (3.2%) and in 19 of 750 vaccine recipients (2.5%), for an efficacy of 21.9% (95% confidence interval [CI], −49.9 to 59.8). Among the 42 participants with Covid-19, 39 cases (92.9%) were caused by the B.1.351 variant; vaccine efficacy against this variant, analyzed as a secondary end point, was 10.4% (95% CI, −76.8 to 54.8).
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