tetano
Editor, Senior Moderator
Nat Commun
. 2024 Feb 20;15(1):1553.
doi: 10.1038/s41467-024-45404-x. Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge
Ching-Lin Hsieh[SUP] #[/SUP][SUP] 1 [/SUP], Sarah R Leist[SUP] #[/SUP][SUP] 2 [/SUP], Emily Happy Miller[SUP] 3 4 [/SUP], Ling Zhou[SUP] 1 [/SUP], John M Powers[SUP] 2 [/SUP], Alexandra L Tse[SUP] 3 [/SUP], Albert Wang[SUP] 3 [/SUP], Ande West[SUP] 2 [/SUP], Mark R Zweigart[SUP] 2 [/SUP], Jonathan C Schisler[SUP] 5 [/SUP], Rohit K Jangra[SUP] 3 6 [/SUP], Kartik Chandran[SUP] 3 [/SUP], Ralph S Baric[SUP] 2 [/SUP], Jason S McLellan[SUP] 7 [/SUP]
Affiliations
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.
. 2024 Feb 20;15(1):1553.
doi: 10.1038/s41467-024-45404-x. Prefusion-stabilized SARS-CoV-2 S2-only antigen provides protection against SARS-CoV-2 challenge
Ching-Lin Hsieh[SUP] #[/SUP][SUP] 1 [/SUP], Sarah R Leist[SUP] #[/SUP][SUP] 2 [/SUP], Emily Happy Miller[SUP] 3 4 [/SUP], Ling Zhou[SUP] 1 [/SUP], John M Powers[SUP] 2 [/SUP], Alexandra L Tse[SUP] 3 [/SUP], Albert Wang[SUP] 3 [/SUP], Ande West[SUP] 2 [/SUP], Mark R Zweigart[SUP] 2 [/SUP], Jonathan C Schisler[SUP] 5 [/SUP], Rohit K Jangra[SUP] 3 6 [/SUP], Kartik Chandran[SUP] 3 [/SUP], Ralph S Baric[SUP] 2 [/SUP], Jason S McLellan[SUP] 7 [/SUP]
Affiliations
- PMID: 38378768
- PMCID: PMC10879192
- DOI: 10.1038/s41467-024-45404-x
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.