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November 7, 2024Open Access

A Single Chimeric Spike Antigen Induces Pan-Sarbecovirus Immunity

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Key result

Immunization with the chimeric spike antigen CoVEXS5 elicited broadly cross-reactive neutralizing antibodies and protected mice and hamsters from clinical disease and viral replication after challenge with diverse SARS-CoV-2 variants.

Why the study?

Next-generation vaccines are required to address the evolving nature of SARS-CoV-2 and to protect against emerging pandemic threats from other coronaviruses by eliciting broad protection.

Population

Mice and hamsters

Comparison

CoVEXS5 in squalene emulsion adjuvant vs NVX-CoV2373 vaccine boost

Design

Preclinical animal study

Authors

CCClaudio CounoupasThe University of SydneyPPPaco PinoExcell Research (United States)JAJoshua ArmitanoUniversity of Geneva

Discussion

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Overview

Supports chimeric spike vaccine development for broad sarbecovirus protection; leaves open translation to human efficacy and safety.

Key Points

  • To develop a stable chimeric spike antigen capable of eliciting broad, cross-protective immunity against circulating and emerging sarbecoviruses.
  • Designed a panel of chimeric full-length spike antigens combining mutations from past, circulating, and predicted SARS-CoV-2 variants, identifying lead candidate CoVEXS5 produced in stable CHO cells.
  • Assessed CoVEXS5 formulated with squalene emulsion adjuvant (Sepivac SWE™) against SARS-CoV-2 infection (including Omicron XBB.1.5 challenge) in mice and hamsters.
  • Tested CoVEXS5 as a heterologous booster in mice previously vaccinated with the licensed protein vaccine NVX-CoV2373.
  • CoVEXS5 immunisation reduced clinical disease signs, lung inflammation, and organ viral loads in mice and hamsters challenged with SARS-CoV-2, including the immunoevasive Omicron XBB.1.5 subvariant.
  • Boosting NVX-CoV2373-primed mice with CoVEXS5 augmented T cell immunity and stimulated cross-reactive neutralizing antibodies against three distinct sarbecovirus clades, surpassing the breadth induced by an NVX-CoV2373 booster.

Structured PICO

P
Population
Preclinical study in mice and hamsters evaluating the immunogenicity and protective efficacy of a novel chimeric spike antigen vaccine (CoVEXS5) against diverse SARS-CoV-2 variants and sarbecoviruses.
I
Intervention
CoVEXS5 (chimeric spike antigen) in a squalene emulsion adjuvant (Sepivac SWE™)
C
Comparator
NVX-CoV2373 vaccine (in boosting experiment)
O
Outcome
Clinical disease signs, lung inflammation, and organ viral titres after SARS-CoV-2 infectionsurrogate

A novel chimeric spike antigen vaccine (CoVEXS5) demonstrates broad pan-sarbecovirus immunity and protection against variants like Omicron XBB.1.5 in preclinical models.

Limitations

  • Preclinical animal models may not fully translate to human immunity and efficacy
  • Clinical trials are required to confirm these findings in humans

Cite This Study

Counoupas et al. (2024) studied SARS-CoV-2 infection. CoVEXS5 (chimeric spike antigen CSA05 + Sepivac SWE adjuvant) vs. Sham (PBS) or Novavax NVX-CoV2373 was evaluated on Protection against clinical disease, weight loss, and viral replication after SARS-CoV-2 challenge. Immunization with the chimeric spike antigen CoVEXS5 elicited broadly cross-reactive neutralizing antibodies and protected mice and hamsters from clinical disease and viral replication after challenge with diverse SARS-CoV-2 variants.

synapsesocial.com/papers/6a9b0a0defdbcdb1c5a79eaehttps://doi.org/10.1101/2024.11.06.622391
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Also Consider

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  1. 1Chimeric spike mRNA vaccines protect against Sarbecoviru s challenge in mice2021 · 16 citations
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  5. 5Broad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine2024 · 33 citations