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<p>Next-generation vaccines are essential to address the evolving nature of SARS-CoV-2 and to protect against emerging pandemic threats from other coronaviruses. These vaccines should elicit broad protection, provide long-lasting immunity and ensure equitable access for all populations. In this study, we developed a panel of chimeric, full-length spike antigens incorporating mutations from previous, circulating and predicted SARS-CoV-2 variants. The lead candidate (CoVEXS5) was produced through a high-yield production process in stable CHO cells achieving &gt;95% purity, demonstrated long-term stability and elicited broadly cross-reactive neutralising antibodies when delivered to mice in a squalene emulsion adjuvant (Sepivac SWE™). In both mice and hamsters, CoVEXS5 immunisation reduced clinical disease signs, lung inflammation and organ viral titres after SARS-CoV-2 infection, including following challenge with the highly immunoevasive Omicron XBB.1.5 subvariant. In mice previously primed with a licenced mRNA vaccine (Comirnaty XBB.1.5, termed mRNA-XBB), CoVEXS5 boosting significantly increased neutralising antibody (nAb) levels against viruses from three sarbecoviruses clades. Boosting with CoVEXS5 via systemic delivery elicited CD4+ lung-resident memory T cells, typically associated with mucosal immunisation strategies, which were not detected following mRNA-XBB boosting. Vaccination of hamsters with CoVEXS5 conferred significant protection against weight loss after SARS-CoV-1 challenge, compared to mRNA-XBB immunisation, that correlated with anti-SARS-CoV-1 nAbs in the sera of vaccinated animals. These findings highlight the potential of a chimeric spike antigen, formulated in an open-access adjuvant, as a next-generation vaccine candidate to enhance cross-protection against emerging sarbecoviruses in vaccinated populations globally.</p>

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An adjuvanted chimeric spike antigen boosts lung-resident memory T-cells and induces pan-sarbecovirus protective immunity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月8日

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  • Claudio Counoupas,
  • Elizabeth Chan,
  • Paco Pino,
  • Joshua Armitano,
  • Matt D. Johansen,
  • Lachlan J. Smith,
  • Caroline L. Ashley,
  • Eva Estapé,
  • Jean Troyon,
  • Sibel Alca,
  • Stefan Miemczyk,
  • Nicole G. Hansbro,
  • Gabriella Scandurra,
  • Warwick J. Britton,
  • Thomas Courant,
  • Patrice M. Dubois,
  • Nicolas Collin,
  • V. Krishna Mohan,
  • Philip M. Hansbro,
  • Maria J. Wurm,
  • Florian M. Wurm,
  • Megan Steain,
  • James A. Triccas

摘要

Next-generation vaccines are essential to address the evolving nature of SARS-CoV-2 and to protect against emerging pandemic threats from other coronaviruses. These vaccines should elicit broad protection, provide long-lasting immunity and ensure equitable access for all populations. In this study, we developed a panel of chimeric, full-length spike antigens incorporating mutations from previous, circulating and predicted SARS-CoV-2 variants. The lead candidate (CoVEXS5) was produced through a high-yield production process in stable CHO cells achieving >95% purity, demonstrated long-term stability and elicited broadly cross-reactive neutralising antibodies when delivered to mice in a squalene emulsion adjuvant (Sepivac SWE™). In both mice and hamsters, CoVEXS5 immunisation reduced clinical disease signs, lung inflammation and organ viral titres after SARS-CoV-2 infection, including following challenge with the highly immunoevasive Omicron XBB.1.5 subvariant. In mice previously primed with a licenced mRNA vaccine (Comirnaty XBB.1.5, termed mRNA-XBB), CoVEXS5 boosting significantly increased neutralising antibody (nAb) levels against viruses from three sarbecoviruses clades. Boosting with CoVEXS5 via systemic delivery elicited CD4+ lung-resident memory T cells, typically associated with mucosal immunisation strategies, which were not detected following mRNA-XBB boosting. Vaccination of hamsters with CoVEXS5 conferred significant protection against weight loss after SARS-CoV-1 challenge, compared to mRNA-XBB immunisation, that correlated with anti-SARS-CoV-1 nAbs in the sera of vaccinated animals. These findings highlight the potential of a chimeric spike antigen, formulated in an open-access adjuvant, as a next-generation vaccine candidate to enhance cross-protection against emerging sarbecoviruses in vaccinated populations globally.