Development of T cell antigen-based human coronavirus vaccines against nAb-escaping SARS-CoV-2 variants
Currently approved vaccines have been successful in preventing the severity of COVID-19 and hospitalization. These vaccines primarily induce humoral immune responses; however, highly transmissible and mutated variants, such as the Omicron variant, weaken the neutralization potential of the vaccines, thus, raising serious concerns about their efficacy. Additionally, while neutralizing antibodies (nAbs) tend to wane more rapidly than cell-mediated immunity, long-lasting T cells typically prevent severe viral illness by directly killing infected cells or aiding other immune cells. Importantly, T cells are more cross-reactive than antibodies, thus, highly mutated variants are less likely to escape lasting broadly cross-reactive T cell immunity. Therefore, T cell antigen-based human coronavirus (HCoV) vaccines with the potential to serve as a supplementary weapon to combat emerging SARS-CoV-2 variants with resistance to nAbs are urgently needed. Alternatively, T cell antigens could also be included in B cell antigen-based vaccines to strengthen vaccine efficacy. This review summarizes recent advancements in research and development of vaccines containing T cell antigens or both T and B cell antigens derived from proteins of SARS-CoV-2 variants and/or other HCoVs based on different vaccine platforms.
Highlights
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The extensively studied COVID-19 vaccines that mainly elicit B cell immunity are effective in reducing disease severity and death rates among infected individuals, although they fail to prevent infection and transmission of the SARS-CoV-2 variants, particularly the Omicron and its subvariants, attributed to their S mutations that confer resistance to nAbs.
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In contrast, vaccines that mainly induce T cell immunity (i.e., T cell antigen-based vaccines) are overlooked but are generally equally effective against the original SARS-CoV-2 strain and variants.
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T cell antigen-based vaccines that induce strong T cell immunity are expected to substantially benefit patients with B cell deficiency and other comorbidities.
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The concept of T cell antigen-based HCoV vaccines with the greater breadth to serve as a supplementary weapon, in addition to B cell antigen-based vaccines, is essential to combat global pandemics caused by SARS-CoV-2 variants. Understanding long-lasting memory T cell responses in some convalescent or vaccinated individuals is important for the design and development of T cell antigen-based HCoV vaccines.
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The development of T cell antigen-based HCoV vaccines is necessary to elicit a comprehensive adaptive immune response needed to curb the current pandemic caused by SARS-CoV-2, its variants, and other highly pathogenic HCoVs that may emerge or reemerge in the future.
