Development of antibody resistance in emerging mutant strains of SARS CoV‐2: Impediment for COVID‐19 vaccines

Abstract

Coronavirus disease 2019 (COVID‐19) is caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), a highly infectious agent associated with unprecedented morbidity and mortality. A failure to stop growth of COVID‐19‐linked morbidity rates is caused by SARS‐CoV‐2 mutations and the emergence of new highly virulent SARS‐CoV‐2 strains. Several acquired SARS‐CoV‐2 mutations reflect viral adaptations to host immune defence. Mutations in the virus Spike‐protein were associated with the lowered effectiveness of current preventive therapies, including vaccines. Recent in vitro studies detected diminished neutralisation capacity of vaccine‐induced antibodies, which are targeted to bind Spike receptor‐binding and N‐terminal domains in the emerging strains. Lower than expected inhibitory activity of antibodies was reported against viruses with E484K Spike mutation, including B.1.1.7 (UK), P.1 (Brazil), B.1.351 (South African), and new Omicron variant (B.1.1.529) with E484A mutation. The vaccine effectiveness is yet to be examined against new mutant strains of SARS‐CoV‐2 originating in Europe, Nigeria, Brazil, South Africa, and India. To prevent the loss of anti‐viral protection in vivo, often defined as antibody resistance, it is required to target highly conserved viral sequences (including Spike protein) and enhance the potency of antibody cocktails. In this review, we assess the reported mutation‐acquiring potential of coronaviruses and compare efficacies of current COVID‐19 vaccines against ‘parent’ and ‘mutant’ strains of SARS‐CoV‐2 (Kappa (B.1.617.1), Delta (B.1.617.2), and Omicron (B.1.1.529)).

An Engineered IgG–VHH Bispecific Antibody against SARS‐CoV‐2 and Its Variants

“…The E484 mutation has been identified as an escape mutation that emerges in several SARS‐CoV‐2 variants of concern. [ 22 ] Moreover, it has been proven that the E484 site tends to have a striking effect on binding and neutralization, especially on RBD‐targeted antibodies, which commonly use heavy‐chain germline IGHV3‐53/3‐66 and are often E484‐targeted. [ 23 ] Thus, subsequent SARS‐CoV‐2 neutralizing antibody therapeutic and vaccine strategies should be engineered to circumvent the escape of variants caused by mutations in these important interaction sites, such as E484.…”

Targeting RNA G-quadruplex with repurposed drugs blocks SARS-CoV-2 entry

“…Indeed, the emergence of SARS-CoV-2 VOCs represents as a major challenge for direct-acting antivirals. For example, the P.1 (gamma) and B.1.135 (beta) VOCs with S protein mutations markedly impaired the neutralizing capacity of the antibody cocktail (bamlanivimab and etesevimab) [ 41 ], while the currently dominating B.1.1.529 (omicron) VOC may reduce the efficacy of most monoclonal antibody treatments [ 42 ]. Conversely, host-directed therapies that target components of the host cell are not susceptible to virus mutations, making them more advantageous than direct-acting antivirals for harnessing VOCs.…”

A SARS-CoV-2 neutralizing antibody discovery by single cell sequencing and molecular modeling

“…With the emergence of SARS-CoV-2 mutations, several neutralizing antibodies have displayed declined protection, which is called antibody resistance [ 41 ] . It is of great significance to develop more powerful antibodies, but this is hard for traditional methods in a limited time.…”