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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 #COVID19 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.


  • 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.

  • 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.

  • T cell antigen-based vaccines that induce strong T cell immunity are expected to substantially benefit patients with B cell deficiency and other comorbidities.

  • 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.

  • 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.

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