Given that cellular immunity may be critical for halting the SARS-CoV-2 infection, T-cell response to the new variants should be monitored

Given that cellular immunity may be critical for halting the SARS-CoV-2 infection, T-cell response to the new variants should be monitored. the duration of immune responses after natural infection or vaccination and shed light on the factors that may affect the immunity induced by the vaccines, such as special disease conditions, sex, and pre-existing immunity, with the aim of aiding in combating COVID-19 and distributing SARS-CoV-2 vaccines under Masupirdine mesylate the prevalence of diverse SARS-CoV-2 variants. Subject terms: Vaccines, Infection Introduction A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), initiated the coronavirus Masupirdine mesylate disease 2019 (COVID-19) pandemic in 20191C4. The global spread of COVID-19 results in the devastating loss of lives and economic well-being. Although control measures such as the use of facemasks, social distancing, and isolation play a role in limiting the transmission of SARS-CoV-2, they cannot impede the spread of COVID-19. Thus, vaccines are developed and rollout globally to reduce the morbidity and mortality associated with COVID-19, with several vaccines granted an Emergency Use Authorization in some countries. SARS-CoV-2 belongs to the genus and encodes multiple non-structural proteins (nsp; nsp1Cnsp10 and nsp12Cnsp16), four structural proteins (membrane (M), envelope (E), nucleocapsid (N), and spike (S) proteins), as well as eight accessory proteins5. The SARS-CoV-2 S protein is essential for successful invasion of the human body and consists of two subunits; S1, which binds to the angiotensin-converting enzyme II (ACE2), and S2, which is responsible for membrane fusion6C8. The S1 subunit is further divided into an N-terminal domain (NTD) and a receptor-binding domain (RBD). Notably, some of the nucleic, vector, and subunit vaccines focus on the viral S protein, whereas inactivated and live-attenuated vaccines are based on the whole virus9. As of 23 September 2021, 121 potential vaccine candidates are in clinical trials and a further 194 candidates are in preclinical testing. Several vaccines, like BNT162b2 and mRNA-1273, exhibited high efficacy in phase 3 clinical trials. However, the emergence of novel circulating mutants has raised concerns about the efficacy of these vaccines. SARS-CoV-2 variants, such as the alpha and beta variants, have spread fast and aggravated the pandemic10,11. Thus, a cohort of scientists are exploring whether the SARS-CoV-2 variants impair the neutralization of convalescent serum Masupirdine mesylate or current vaccines. Moreover, the immune changes in individuals after natural infection or vaccination are being monitored to better understand the kinetics of immune responses against SARS-CoV-2. In this review, we presented mutational hotspots, the characteristics of SARS-CoV-2 variants, and their abilities to resist neutralization. We also summarized the changes in an individuals immunity after being infected or vaccinated and discussed the factors that might influence vaccine efficacy. We hope our review will offer clues for exploring the mechanisms used by SARS-CoV-2 variants to evade the vaccine-induced immunity, as well as aid in the distribution of SARS-CoV-2 vaccines, especially to those with a high risk of COVID-19. Mutational hotspots of SARS-CoV-2 The SARS-CoV-2 variants carry a distinctive constellation of mutations and some mutations are of virological importance. The epitopes in RBD account for ~90% of the neutralizing activity of sera from individuals previously infected with SARS-CoV-212. Mutations in the RBD of SARS-CoV-2 variants influence the neutralization activity of antibodies in diverse ways (Fig. ?(Fig.1).1). The E484K mutation, which occurred in both the beta and gamma variants, diminished the salt-bridge and/or hydrogen-bonding interactions with some antibodies (e.g., BD368-2, P5A-1B9, P2B-2F6, and CV07-270), rendering these antibodies ineffective against these two variants13. The E484K mutants also showed resistance to the C121 or C144, 2B04, 1B07, REGN-10989, REGN-10934 antibodies, and polyclonal human convalescent sera14C17. Although E484K lowered the neutralizing activity of antibody P2C-1F11, there were additional interactions between N417 or Y501 mutations and P2C-1F11, partly resulting in the retained binding and neutralization of P2C-1F11 against SARS-CoV-2 variants containing the K417N/E484K/N501Y mutations13. Some mutations also LAMP3 enhanced binding affinity to human ACE2, which may diminish the binding and neutralizing activities of antibodies. N439K was a prevalent mutation with increased ACE2-binding avidity and reduced some monoclonal antibody and polyclonal serum-mediated neutralization18. S477N, E484K, and N501Y, which were present in the alpha, beta, and gamma variants, were also able to enhance binding affinity to ACE2, resulting in the increased transmissibility of those variants in the population19C21. E484K or N501Y mutations alone were found to increase the affinity of the RBD to ACE2, whereas the combination of K417N, E484K, and N501Y caused the highest degree of RBD conformational alterations, which may perturb the antigen recognition22. The L452R mutation, included in the S protein of the delta and kappa variants, increased viral replication kinetics compared with the wild-type virus23. The L452R mutation also impaired neutralization mediated by some clinical Masupirdine mesylate antibodies due to steric alteration.