SARS-COV-2 Variants: Differences and Potential of Immune Evasion

Abstract

The structural spike (S) glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) plays an essential role in infection and is an important target for neutralizing antibody recognition. Mutations in the S gene can generate variants of concern (VOCs), which improve “viral fitness” through selective or survival advantages, such as increased ACE-2 receptor affinity, infectivity, viral replication, higher transmissibility, resistance to neutralizing antibodies and immune escape, increasing disease severity and reinfection risk. Five VOCs have been recognized and include B.1.1.7 (U.K.), B.1.351 (South Africa), P.1 (Brazil), B.1.617.2 (India), and B.1.1.529 (multiple countries). In this review, we addressed the following critical points concerning VOCs: a) characteristics of the SARS-CoV-2 VOCs with mutations in the S gene; b) possible evasion of variants from neutralizing antibodies generated through vaccination, previous infection, or immune therapies; c) potential risk of new pandemic waves induced by the variants worldwide; and d) perspectives for further studies and actions aimed at preventing or reducing the impact of new variants during the current COVID-19 pandemic.

Rapid hypermutation B cell trajectory recruits previously primed B cells upon third SARS-CoV-2 mRNA vaccination

“…In January 2022, Omicron replaced Delta as the dominant variant accompanied by a record of 15 million new COVID-19 cases worldwide in a single week. Both Delta and Omicron variants cause concerns also in fully vaccinated populations since the current vaccines are targeted at the ancestral SARS-CoV-2 strain (36–43). In addition, it was also reported that the type and/or sequence of different exposures triggers SARS-CoV-2-directed immune responses varying in specificity and neutralizing potency (44).…”

“…The repertoire space taken up by these vaccine-induced expanding B cell lineages was substantially higher after the third vaccination than after completion of the primary vaccination series (Figure 5B). The stream plots in Figure 5C and Supplementary Figure 1 Both Delta and Omicron variants cause concerns also in fully vaccinated populations since the current vaccines are targeted at the ancestral SARS-CoV-2 strain (36)(37)(38)(39)(40)(41)(42)(43). In addition, it was also reported that the type and/or sequence of different exposures triggers SARS-CoV-2-directed immune responses varying in specificity and neutralizing potency (44).…”

“…Detailed analysis of these maturation trajectories showed that the precursors of highly mutated post-booster clones were either naive or antigen-experienced cells that were mobilized into a secondary round of somatic hypermutation, most likely through a second recruitment to a germinal center. Exemplary mutational trajectories Both Delta and Omicron variants cause concerns also in fully vaccinated populations since the current vaccines are targeted at the ancestral SARS-CoV-2 strain (36)(37)(38)(39)(40)(41)(42)(43). In addition, it was also reported that the type and/or sequence of different exposures triggers SARS-CoV-2-directed immune responses varying in specificity and neutralizing potency (44).…”

COVID-19 Genetic Variants and Their Potential Impact in Vaccine Development

“…Remarkably, a recent study revealed the distribution of the SARS-CoV-2 variants of concerns in several countries, providing a general overview of specific variants globally [ 104 ]. For example, the B.1.1.7 variant rapidly spread to several countries across all continents, while the B.1.351 variant emerged in South Africa in August 2020, rapidly disseminating worldwide, reaching 111 countries, as of 2 September 2021 ( Figure 5 ) [ 104 ].…”

Assessment of BIV1-CovIran inactivated vaccine–elicited neutralizing antibody against the emerging SARS-CoV-2 variants of concern

“…The most important emerging VOCs that were isolated from different parts of the world are Alpha VOC (variant 20I/501Y.V1, lineage B.1.1.7) in United Kingdom (September, 2020), Beta VOC (variant 20H/501Y.V2, lineage B. 1.351) in South Africa (May, 2020), Gamma VOC (variant B.1.1.248, lineage P.1) in Brazil (November, 2020) and Delta VOC (variant B.1.617.2, lineage AY) in India (October, 2020) (3,4).Omicron (B.1.1.529) as the fifth of these variants of concern is characterized by 37 amino acid substitutions in the S protein, 15 of these occurring in the receptor binding domain which made omicron to evade neutralizing antibody stimulated via past infection or vaccination (5,6). Omicron replicated rapidly than all other SARS-CoV-2 in the upper respiratory system but displayed less efficient replication and fusion activity at lower respiratory system (7).…”