Covid-19 vaccines and variants of concern: A review

Abstract

Since the outbreak of coronavirus disease 2019 (Covid-19) in December 2019, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the number of confirmed infections has risen to more than 242 million worldwide, with nearly 5 million deaths. Currently, nine Covid-19 vaccine candidates based on the original Wuhan-Hu-1 strain are at the forefront of vaccine research. All nine had an efficacy over 50% against symptomatic Covid-19 disease: NVX-CoV2373 (∼96%), BNT162b2 (∼95%), mRNA-1273 (∼94%), Sputnik V (∼92%), AZD1222 (∼81%), BBIBP-CorV (∼79%), Covaxin (∼78%), Ad26.CoV.S (∼66%) and CoronaVac (∼51%). However, vaccine efficacy (VE) can be jeopardised by the rapid emergence and spread of SARS-CoV-2 variants of concern (VOCs) that could escape from neutralising antibodies and/or cell-mediated immunity. Rare adverse events have also been reported soon after administration of viral vector and mRNA vaccines. Although many Covid-19 vaccines have been developed, additional effective vaccines are still needed to meet the global demand. Promising Covid-19 vaccines such as WIBP-CorV, AD5-nCOV, ZyCoV-D, CVnCoV, EpiVacCorona and ZF2001 have advanced to clinical studies. This review describes the most relevant mutations in the SARS-CoV-2 spike protein, discusses VE against VOCs, presents rare adverse events after Covid-19 vaccination and introduces some promising Covid-19 vaccine candidates.

Keywords: Covid-19 vaccines; SARS-CoV-2; rare adverse events; vaccine efficacy; variants of concern.

FIGURE 1

Structure and genomic characteristics of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). (a) Schematic representation of the SARS‐CoV‐2 structure showing the exterior envelope (E), membrane (M), spike glycoprotein (S), nucleocapsid (N) and RNA viral genome. (b) Schematic representation of the SARS‐CoV‐2 genome organisation (∼30 kb) showing the two large open reading frames ORF1a and ORF1b, which encode the non‐structural proteins, separated by the ribosome frameshift site. Genes encoding the structural proteins are as follows: spike (S), envelope (E), membrane (M) and nucleocapsid (N). The S glycoprotein consists of two subunits. Subunit S1 contains an N‐terminal domain (NTD) and the receptor‐binding domain (RBD). Subunit S2 includes an internal membrane fusion peptide (FP), two heptapeptide repeat sequences (HR1 and HR2), a membrane‐proximal external region and a transmembrane domain (TM). (c) Schematic representation of SARS‐CoV‐2 spike protein showing the two subunits: S1 and S2. (d) Crystallographic structure of the SARS‐CoV‐2 spike protein (PDB ID:6VXX). Figure generated with BioRender

FIGURE 2

Important amino acid mutations in the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) spike glycoprotein rendering variants of concern shown on an SARS‐CoV‐2 genome representation, and focused on the spike protein. (a) Important amino acid substitutions in the spike glycoprotein of the Alpha variant, B.1.1.7 lineage. (b) Notable spike mutations of the SARS‐CoV‐2 Beta variant, B.1.351 lineage. (c) Relevant amino acid substitutions in the spike of the SARS‐CoV‐2 Gamma variant, P.1 lineage. (d) Relevant amino acid substitutions in the spike of the SARS‐CoV‐2 Delta variant, B.1.617.2 lineage. Figure generated with BioRender. FP, fusion peptide; NTD, N‐terminal domain; RBD, receptor‐binding domain; TM, transmembrane domain

FIGURE 3

Major vaccine technology platforms are exploited for designing Covid‐19 vaccines. Inactivated Covid‐19 vaccines involve severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) strains inactivated by radiation or high temperatures. Viral vector Covid‐19 vaccines utilise an adenovirus that incorporate genetic material of the target virus. RNA‐based Covid‐19 vaccines are made of RNA encoding the target antigen and encapsulated within lipid nanoparticles. DNA‐based Covid‐19 vaccines are made of a DNA plasmid encoding the target antigen and generally administered by electroporation. The subunit Covid‐19 vaccines contain purified antigens of SARS‐CoV‐2 that stimulate the immune system. Figure generated with BioRender