SARS-CoV-2 epitopes inform future vaccination strategies

Abstract

All currently approved COVID-19 vaccines utilize the spike protein as their immunogen. SARS-CoV-2 variants of concern (VOCs) contain mutations in the spike protein, enabling them to escape infection- and vaccination-induced immune responses to cause reinfection. New vaccines are hence being researched intensively. Studying SARS-CoV-2 epitopes is essential for vaccine design, as identifying targets of broadly neutralizing antibody responses and immunodominant T-cell epitopes reveal candidates for inclusion in next-generation COVID-19 vaccines. We summarize the major studies which have reported on SARS-CoV-2 antibody and T-cell epitopes thus far. These results suggest that a future of pan-coronavirus vaccines, which not only protect against SARS-CoV-2 but numerous other coronaviruses, may be possible. The T-cell epitopes of SARS-CoV-2 have gotten less attention than neutralizing antibody epitopes but may provide new strategies to control SARS-CoV-2 infection. T-cells target many SARS-CoV-2 antigens other than spike, recognizing numerous epitopes within these antigens, thereby limiting the chance of immune escape by VOCs that mainly possess spike protein mutations. Therefore, augmenting vaccination-induced T-cell responses against SARS-CoV-2 may provide adequate protection despite broad antibody escape by VOCs.

Antigen clustering effect on immunogenicity in prefusion-stabilized spike-based COVID-19 vaccines

“…Given these, we speculate that stabilized monovalent spike trimers may crosslink BCRs through simultaneous recognition of epitopes by multiple BCRs, providing an optimal BCR signal that effectively induces the B cell response. Indeed, neutralizing mAbs-targeted epitopes have been characterized in a variety of locations on the spike protein, including the receptorbinding domain, the adjacent N-terminal domain, and the C-terminal S2 domain (Shafqat et al, 2022).…”

How Neutrophils Shape the Immune Response: Reassessing Their Multifaceted Role in Health and Disease

“…A central mechanism by which SARS-CoV-2 causes severe disease is by delaying the production of type I IFNs, which are key initiators of antiviral immunity [188][189][190]. This delay in type I IFN responses and T-cell recruitment is associated with an exaggerated myeloid cell-particularly neutrophil-response [191][192][193]. Salient features of severe COVID-19 include an elevated neutrophil-to-lymphocyte ratio [194], the emergence of immature neutrophil populations in both the blood and lungs [195][196][197], and activated pro-inflammatory neutrophil phenotypes in both the circulation and lungs with an enhanced production of TNF-α, IL-6, CXCL8, alarmins like calprotectin (SA100A8/A9), and NETs [198][199][200].…”

Bioinformatic identification of Endemic Coronaviruses’ epitopes in SARS-CoV-2 genomes isolated in Kenya

“…Additionally, the identi cation of a conserved SARS-CoV-2 S2 spike epitope that elicited cross-reactive antibody responses to related coronaviruses and host bacteria underscores the potential for broad coronavirus therapeutics and vaccines 18 . Therefore these shared epitopes between SARS-CoV-2 and endemic coronaviruses highlight the potential for crossimmunity and the development of vaccines that could offer broad protection against current and future coronavirus outbreaks [19][20][21] .…”