Immune Evasion of SARS-CoV-2 Emerging Variants: What Have We Learnt So Far?

Abstract

Despite the slow evolutionary rate of SARS-CoV-2 relative to other RNA viruses, its massive and rapid transmission during the COVID-19 pandemic has enabled it to acquire significant genetic diversity since it first entered the human population. This led to the emergence of numerous variants, some of them recently being labeled “variants of concern” (VOC), due to their potential impact on transmission, morbidity/mortality, and the evasion of neutralization by antibodies elicited by infection, vaccination, or therapeutic application. The potential to evade neutralization is the result of diversity of the target epitopes generated by the accumulation of mutations in the spike protein. While three globally recognized VOCs (Alpha or B.1.1.7, Beta or B.1.351, and Gamma or P.1) remain sensitive to neutralization albeit at reduced levels by the sera of convalescent individuals and recipients of several anti-COVID19 vaccines, the effect of spike variability is much more evident on the neutralization capacity of monoclonal antibodies. The newly recognized VOC Delta or lineage B.1.617.2, as well as locally accepted VOCs (Epsilon or B.1.427/29-US and B1.1.7 with the E484K-UK) are indicating the necessity of close monitoring of new variants on a global level. The VOCs characteristics, their mutational patterns, and the role mutations play in immune evasion are summarized in this review.

Emergence of Multiple SARS-CoV-2 Antibody Escape Variants in an Immunocompromised Host Undergoing Convalescent Plasma Treatment

“…After a year of the COVID-19 pandemic, with >200 million global cases and 4 million deaths, the world is now focused on the biological consequences of the distribution of vaccines and the spread of “variants of concern” (VOCs). Four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) VOCs, i.e., B.1.1.7 (20I/501Y.V1, alpha), B.1.351 (20H/501Y.V2, beta), P1 (20J/501Y.V3, gamma), and B.1.617.2 (delta), carrying the spike protein N501Y mutation emerged in the United Kingdom, South Africa, Brazil, Japan, and India ( 1 – 3 ) and have been associated with high transmissibility due to increased affinity to the angiotensin-converting enzyme 2 (ACE2) receptor. In each of these viruses, the spike protein contains clustered mutations in the N-terminal domain (NTD) and the receptor-binding domain (RBD) (e.g., E484K) regions.…”

Heterologous Hyperimmune Polyclonal Antibodies Against SARS-CoV-2: A Broad Coverage, Affordable, and Scalable Potential Immunotherapy for COVID-19

“…Another obstacle for COVID-19 therapy with mAbs is the emergence of viral variants harboring changes in the receptorbinding domain (RBD) of the S1 glycoprotein (13). The variants of concern (VoC) exhibit enhanced transmissibility or virulence, circulate worldwide, and include those designated as alpha, beta, epsilon, gamma, and delta, first detected in the UK, South Africa, Brazil, USA, and India, respectively (13). Therapeutic mAbs, and antibodies in the plasma of vaccinated or convalescent individuals, fail to neutralize VoC efficiently (13)(14)(15)(16)(17).…”

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

“…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 ]. Third, it takes a long time for the vaccine development, clinical trial, and authorized application of the vaccine.…”