The Impact of Evolving SARS-CoV-2 Mutations and Variants on COVID-19 Vaccines

Abstract

The emergence of several new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in recent months has raised concerns around the potential impact on ongoing vaccination programs. Data from clinical trials and real-world evidence suggest that current vaccines remain highly effective against the alpha variant (B.1.1.7), while some vaccines have reduced efficacy and effectiveness against symptomatic disease caused by the beta variant (B.1.351) and the delta variant (B.1.617.2); however, effectiveness against severe disease and hospitalization caused by delta remains high. Although data on the effectiveness of the primary regimen against omicron (B.1.1.529) are limited, booster programs using mRNA vaccines have been shown to restore protection against infection and symptomatic disease (regardless of the vaccine used for the primary regimen) and maintain high effectiveness against hospitalization. However, effectiveness against infection and symptomatic disease wanes with time after the booster dose. Studies have demonstrated reductions of varying magnitude in neutralizing activity of vaccine-elicited antibodies against a range of SARS-CoV-2 variants, with the omicron variant in particular exhibiting partial immune escape. However, evidence suggests that T-cell responses are preserved across vaccine platforms, regardless of variant of concern. Nevertheless, various mitigation strategies are under investigation to address the potential for reduced efficacy or effectiveness against current and future SARS-CoV-2 variants, including modification of vaccines for certain variants (including omicron), multivalent vaccine formulations, and different delivery mechanisms.

Keywords: COVID-19; SARS-CoV-2; mutation; vaccines; variant.

FIG 1

(A) Location of spike protein mutations in SARS-CoV-2 variants alpha, beta, gamma, delta, lambda, mu, and omicron (1); (B) 3D structure of the spike protein of SARS-CoV-2 variants alpha, beta, gamma, delta, and omicron in comparison with an ancestral virus created using PyMOL molecular graphic system version 2.3.2 (https://pymol.org). C, cleavage site (residues 681–685); CD, connector domain; CH, central helix; CT, cytoplasmic domain fusion; CTD, C-terminal domain; FP, fusion protein; HR, heptad repeat; SP, signal peptide; TM, transmembrane domain. ^†Disputed with mutation at same site. ^‡Based on BA.1 lineage, which is part of the larger group of omicron/B.1.1.529 sequences. Exact position and number of mutations may differ according to source. Structure of spike glycoprotein in A based on Cai et al. (186). Mutations with known or proposed biological significance shown in red. Images in B are based on protein data bank (PDB) entry 6XR8 (https://www.rcsb.org/structure/6xr8). The structure contains D614 but has better solved sequence coverage than other entries although residue P681 is missing and not labeled where mutated in a VOC. Beta: R226I is missing and is not labeled. Gamma: T1072I (in seq is E1072). Omicron: N679K and N969K are missing and not labeled. Domain coloring of spike subunit as follows: NTD: green; RBD: blue; all others including entire subunits 2 and 3: cyan. Mutations are shown in color of function (red: known; black: unknown) and are shown in a single subunit for clarity.