Variants of SARS-CoV-2: Influences on the Vaccines’ Effectiveness and Possible Strategies to Overcome Their Consequences

Abstract

The immune response elicited by the current COVID-19 vaccinations declines with time, especially among the immunocompromised population. Furthermore, the emergence of novel SARS-CoV-2 variants, particularly the Omicron variant, has raised serious concerns about the efficacy of currently available vaccines in protecting the most vulnerable people. Several studies have reported that vaccinated people get breakthrough infections amid COVID-19 cases. So far, five variants of concern (VOCs) have been reported, resulting in successive waves of infection. These variants have shown a variable amount of resistance towards the neutralising antibodies (nAbs) elicited either through natural infection or the vaccination. The spike (S) protein, membrane (M) protein, and envelope (E) protein on the viral surface envelope and the N-nucleocapsid protein in the core of the ribonucleoprotein are the major structural vaccine target proteins against COVID-19. Among these targets, S Protein has been extensively exploited to generate effective vaccines against COVID-19. Hence, amid the emergence of novel variants of SARS-CoV-2, we have discussed their impact on currently available vaccines. We have also discussed the potential roles of S Protein in the development of novel vaccination approaches to contain the negative consequences of the variants’ emergence and acquisition of mutations in the S Protein of SARS-CoV-2. Moreover, the implications of SARS-CoV-2’s structural proteins were also discussed in terms of their variable potential to elicit an effective amount of immune response.

Unravelling Insights into the Evolution and Management of SARS-CoV-2

“…There are three stages of SARS-CoV-2 clinical pathology: mild, severe, and critical, with critical being the stage that results in mortality [45]. Adults who are infected typically show no symptoms or only mild, temporary symptoms, whereas those who show symptoms are most contagious the day before symptoms appear [46,47].…”

“…Current COVID-19 vaccines induce immune responses against the viral spike protein or its subunits, thereby preventing cellular entry [162]. The emergence of SARS-CoV-2 variants poses challenges, prompting the design of a peptide-based vaccine with epitopes targeting pathogenic proteins [45]. Computational methods, reverse vaccinology, and immunoinformatics guide the creation of a multi-epitope-based peptide vaccine by considering mutations in spike glycoprotein.…”

Interface design of SARS-CoV-2 symmetrical nsp7 dimer and machine learning-guided nsp7 sequence prediction reveals physicochemical properties and hotspots for nsp7 stability, adaptation, and therapeutic design

“…8 This genetic diversity has given rise to various SARS-CoV-2 lineages and variants, some of which have garnered substantial attention due to their potential impact on transmissibility, severity, vaccine effectiveness, and diagnostic accuracy. 9 Variants such as alpha, beta, gamma, delta, omicron and recently identified sub-variants like JN.1 have specific mutations in the spike protein and other regions of the genome, which have raised concerns about their ability to evade immunity, influence viral replication, and alter the course of the pandemic. 10 These variants mostly emerged from mutations in the intracellular proteins of SARS-CoV-2, and to fully grasp the impact of these variants, it is crucial to investigate the molecular mechanisms that underpin viral replication, immune evasion, and pathogenesis.…”

Immunomodulatory approaches in managing lung inflammation in COVID‐19: A double‐edge sword

“…Furthermore, the duration of protection imparted by a vaccine is yet to be determined. The emergence of highly transmissible variant(s) of concern (VoC) of SARS‐CoV‐2, such as Delta and Omicron, owing to mutations in the gene that encodes for spike glycoprotein has raised serious concerns about the effectiveness of available vaccines as the outbreaks have been seen in the vaccinated population 9,10 . Additionally, the effectiveness of majorly available monoclonal antibodies (MABs) against the highly mutated variant that is, Omicron raised a need to develop the alternative medications to treat COVID‐19 11 .…”

“…The emergence of highly transmissible variant(s) of concern (VoC) of SARS‐CoV‐2, such as Delta and Omicron, owing to mutations in the gene that encodes for spike glycoprotein has raised serious concerns about the effectiveness of available vaccines as the outbreaks have been seen in the vaccinated population. 9 , 10 Additionally, the effectiveness of majorly available monoclonal antibodies (MABs) against the highly mutated variant that is, Omicron raised a need to develop the alternative medications to treat COVID‐19. 11 Adverse events like cytokine storm have been observed following receipt of second dose of COVID‐19 vaccination in four cases, showing immune dysregulation might have occurred, 12 suggesting further the need of immunomodulatory approaches (Table 1 ).…”