SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern

Abstract

A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), originally detected in California, carries spike glycoprotein mutations S13I in the signal peptide, W152C in the N-terminal domain (NTD), and L452R in the receptor-binding domain (RBD). Plasma from individuals vaccinated with a Wuhan-1 isolate-based mRNA vaccine or convalescent individuals exhibited neutralizing titers, which were reduced 2-3.5 fold against the B.1.427/B.1.429 variant relative to wildtype pseudoviruses. The L452R mutation reduced neutralizing activity of 14 out of 34 RBD-specific monoclonal antibodies (mAbs). The S13I and W152C mutations resulted in total loss of neutralization for 10 out of 10 NTD-specific mAbs since the NTD antigenic supersite was remodeled by a shift of the signal peptide cleavage site and formation of a new disulphide bond, as revealed by mass spectrometry and structural studies.

An intranasal vaccine durably protects against SARS-CoV-2 variants in mice

“…Neutralizing antibody titers against WA1/2020 and three other SARS-CoV-2 strains with spike proteins from B.1.351 and B.1.1.28 variants or a B.1.617.1 isolate were measured by FRNT assay (Figures 4C-4E and S2). High levels of neutralizing antibody against WA1/2020 were induced after a single IN dose of ChAd-SARS-CoV-2-S. As seen with vaccine-induced human sera against some variant viruses (Chen et al, McCallum et al, 2021;Tada et al, 2021;Wang et al, 2021aWang et al, , 2021bWibmer et al, 2021), we observed decreases in neutralizing titers against Wash-B.1.351 (5-fold, p < 0.0001; Figure 4C), Wash-B.1.1.28 (3-fold, p < 0.0001; Figure 4D), and B.1.617.1 (7-fold, p < 0.01, Figure 4E) strains compared to WA1/2020. To assess the durability of humoral responses, a separate cohort of K18-hACE2 mice was immunized via the IN route, and serum samples were collected at 9 months.…”

Reduced neutralizing activity of post-SARS-CoV-2 vaccination serum against variants B.1.617.2, B.1.351, B.1.1.7+E484K and a sub-variant of C.37

“…Since the detection of these first variants, several other variants of interest (VoIs) and variants of concern (VoCs) have spread locally as well as globally. These include B.1.526 (Iota) which emerged in New York City and comprises three different sub-lineages 11,12 , B.1.427/B.1.429 (Epsilon) which emerged in California, 13 C.37 (Lambda) which emerged in Peru, 3 B.1.617.2 (Delta) and B.1.617.1 (Kappa) which emerged in India, 14 B.1.1.7+E484K (Alpha) which was detected in several countries, as well as A.23.1 which was first detected in Uganda. 15 Several of these lineages are in decline, including B.1.526 and B.1.427/B.1.429 while others such as B.1.617.2 are increasing in prevalence.…”

Possible Targets of Pan-Coronavirus Antiviral Strategies for Emerging or Re-Emerging Coronaviruses

“…First, because of the low conservation of virus antigens in the same viral family, especially key antigenic determinants, few conserved protective cross-reactive antigens have been identified. Second, the continuous mutations of the coronavirus lead to the immune evasion of the viruses and reduce the efficacy of existing vaccines or universal vaccines, which have also been identified in the SARS-CoV-2 variants of concern (VOCs), including Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) [ 7 , 8 , 9 , 10 ]. Notably, the Delta variant SARS-CoV-2, which is characterized by spike mutations T19R, G142D, Δ157-158, L452R, T478K, D614G, P681R, and D950N, is rapidly outcompeting other VOCs and has become the dominant variant in past months [ 8 , 11 ].…”