Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge

Hsieh, Ching-Lin; Leist, Sarah R.; Miller, Emily Happy; Zhou, Ling; Powers, John M.; Tse, Alexandra L.; Wang, Albert; West, Ande; Zweigart, Mark R.; Schisler, Jonathan C.; Jangra, Rohit K.; Chandran, Kartik; Baric, Ralph S.; McLellan, Jason S.

doi:10.1038/s41467-024-45404-x

Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge

Journal Article · Mon Feb 19 23:00:00 EST 2024 · Nature Communications

DOI:https://doi.org/10.1038/s41467-024-45404-x· OSTI ID:2469548

^[1]; ^[2]; Miller, Emily Happy ^[3]; Zhou, Ling ^[1]; ^[2]; ^[3]; Wang, Albert ^[3]; West, Ande ^[2]; Zweigart, Mark R. ^[2]; ^[2]; Jangra, Rohit K. ^[4]; Chandran, Kartik ^[3]; ^[2]; ^[1]

University of Texas, Austin, TX (United States)
University of North Carolina, Chapel Hill, NC (United States)
Albert Einstein College of Medicine, Bronx, NY (United States)
Louisiana State University Health Sciences Center, Shreveport, LA (United States); Albert Einstein College of Medicine, Bronx, NY (United States)

Ever-evolving SARS-CoV-2 variants of concern (VOCs) have diminished the effectiveness of therapeutic antibodies and vaccines. Developing a coronavirus vaccine that offers a greater breadth of protection against current and future VOCs would eliminate the need to reformulate COVID-19 vaccines. Here, we rationally engineer the sequence-conserved S2 subunit of the SARS-CoV-2 spike protein and characterize the resulting S2-only antigens. Structural studies demonstrate that the introduction of interprotomer disulfide bonds can lock S2 in prefusion trimers, although the apex samples a continuum of conformations between open and closed states. Immunization with prefusion-stabilized S2 constructs elicits broadly neutralizing responses against several sarbecoviruses and protects female BALB/c mice from mouse-adapted SARS-CoV-2 lethal challenge and partially protects female BALB/c mice from mouse-adapted SARS-CoV lethal challenge. These engineering and immunogenicity results should inform the development of next-generation pan-coronavirus therapeutics and vaccines.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH); Bill & Melinda Gates Foundation; Cancer Prevention and Research Institute of Texas (CPRIT)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2469548

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 15; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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