Prefusion-stabilized SARS-CoV-2 S2-only Antigen Provides Protection Against SARS-CoV-2 Challenge

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Feb 20

PMID 38378768

Authors

Ching-Lin Hsieh

Sarah R Leist

Emily Happy Miller

Ling Zhou

John M Powers

Alexandra L Tse

Albert Wang

Ande West

Mark R Zweigart

Jonathan C Schisler

Rohit K Jangra

Kartik Chandran

Ralph S Baric

Jason S McLellan

Affiliations

Soon will be listed here.

Abstract

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.

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