An adjuvanted chimeric spike antigen boosts lung-resident memory T-cells and induces pan-sarbecovirus protective immunity
Abstract 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 thi...
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Nature Portfolio
2025-05-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01144-7 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Claudio Counoupas |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-80e7a4080d9149149769ab2dbe6d7ccf |
| institution | DOAJ |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-80e7a4080d9149149769ab2dbe6d7ccf2025-08-20T03:09:35ZengNature Portfolionpj Vaccines2059-01052025-05-0110111110.1038/s41541-025-01144-7An adjuvanted chimeric spike antigen boosts lung-resident memory T-cells and induces pan-sarbecovirus protective immunityClaudio Counoupas0Elizabeth Chan1Paco Pino2Joshua Armitano3Matt D. Johansen4Lachlan J. Smith5Caroline L. Ashley6Eva Estapé7Jean Troyon8Sibel Alca9Stefan Miemczyk10Nicole G. Hansbro11Gabriella Scandurra12Warwick J. Britton13Thomas Courant14Patrice M. Dubois15Nicolas Collin16V. Krishna Mohan17Philip M. Hansbro18Maria J. Wurm19Florian M. Wurm20Megan Steain21James A. Triccas22Sydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of SydneySydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of SydneyExcellGene SAExcellGene SACentre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life SciencesSydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of SydneySydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of SydneyExcellGene SAExcellGene SASydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of SydneyCentre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life SciencesCentre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life SciencesSydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of SydneyCentre for Infection and Immunity, Centenary Institute, The University of SydneyVaccine Formulation InstituteVaccine Formulation InstituteVaccine Formulation InstituteBharat Biotech International Limited, Genome ValleyCentre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life SciencesExcellGene SAExcellGene SASydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of SydneySydney Infectious Diseases Institute (Sydney ID), Faculty of Medicine and Health, The University of SydneyAbstract 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.https://doi.org/10.1038/s41541-025-01144-7 |
| spellingShingle | 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 An adjuvanted chimeric spike antigen boosts lung-resident memory T-cells and induces pan-sarbecovirus protective immunity npj Vaccines |
| title | An adjuvanted chimeric spike antigen boosts lung-resident memory T-cells and induces pan-sarbecovirus protective immunity |
| title_full | An adjuvanted chimeric spike antigen boosts lung-resident memory T-cells and induces pan-sarbecovirus protective immunity |
| title_fullStr | An adjuvanted chimeric spike antigen boosts lung-resident memory T-cells and induces pan-sarbecovirus protective immunity |
| title_full_unstemmed | An adjuvanted chimeric spike antigen boosts lung-resident memory T-cells and induces pan-sarbecovirus protective immunity |
| title_short | An adjuvanted chimeric spike antigen boosts lung-resident memory T-cells and induces pan-sarbecovirus protective immunity |
| title_sort | adjuvanted chimeric spike antigen boosts lung resident memory t cells and induces pan sarbecovirus protective immunity |
| url | https://doi.org/10.1038/s41541-025-01144-7 |
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