Highly conserved Betacoronavirus sequences are broadly recognized by human T cells

Area of Science:

• Immunology
• Virology
• Vaccine Development

Background:

• The COVID-19 pandemic underscored the need for vaccines against emerging viral threats, particularly Betacoronaviruses.
• Betacoronaviruses (e.g., SARS-CoV, MERS-CoV, SARS-CoV-2) pose significant risks due to zoonotic potential and genetic diversity.
• T cell immunity offers durable, cross-reactive responses crucial for broad protection.

Purpose of the Study:

• To identify conserved T cell epitope regions (CTERs) within the SARS-CoV-2 proteome.
• To evaluate the cross-reactivity of CTER-specific T cells against other Betacoronaviruses.
• To assess the impact of including non-spike proteins on vaccine-induced cross-immunity.

Main Methods:

• Comprehensive epitope mapping of the SARS-CoV-2 proteome.
• Sequence conservation analyses to identify CTERs.
• Assessment of T cell cross-reactivity and human leukocyte antigen (HLA) coverage.

Main Results:

• Conserved T cell epitope regions (CTERs) constitute 12% of the SARS-CoV-2 proteome.
• SARS-CoV-2 CTER-specific T cells demonstrated cross-reactivity with multiple Betacoronavirus subgenera.
• Inclusion of non-spike protein CTERs significantly improved T cell cross-reactivity and HLA coverage.

Conclusions:

• A multi-antigen vaccine strategy incorporating CTERs from non-spike proteins can broaden cross-reactive immunity against Betacoronaviruses.
• This approach holds promise for developing vaccines effective against a wider range of coronaviruses.
• Findings support the development of next-generation vaccines for pandemic preparedness.