tetano
Editor, Senior Moderator
NPJ Vaccines
. 2025 May 8;10(1):89.
doi: 10.1038/s41541-025-01144-7. An adjuvanted chimeric spike antigen boosts lung-resident memory T-cells and induces pan-sarbecovirus protective immunity
Claudio Counoupas[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Elizabeth Chan[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Paco Pino[SUP] 4 [/SUP], Joshua Armitano[SUP] 4 [/SUP], Matt D Johansen[SUP] 5 [/SUP], Lachlan J Smith[SUP] 1 3 [/SUP], Caroline L Ashley[SUP] 1 3 [/SUP], Eva Estapé[SUP] 4 [/SUP], Jean Troyon[SUP] 4 [/SUP], Sibel Alca[SUP] 1 3 [/SUP], Stefan Miemczyk[SUP] 5 [/SUP], Nicole G Hansbro[SUP] 5 [/SUP], Gabriella Scandurra[SUP] 1 3 [/SUP], Warwick J Britton[SUP] 2 [/SUP], Thomas Courant[SUP] 6 [/SUP], Patrice M Dubois[SUP] 6 [/SUP], Nicolas Collin[SUP] 6 [/SUP], V Krishna Mohan[SUP] 7 [/SUP], Philip M Hansbro[SUP] 5 [/SUP], Maria J Wurm[SUP] 4 [/SUP], Florian M Wurm[SUP] 4 8 [/SUP], Megan Steain[SUP] 1 3 9 [/SUP], James A Triccas[SUP] 10 11 12 13 [/SUP]
Affiliations
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.
. 2025 May 8;10(1):89.
doi: 10.1038/s41541-025-01144-7. An adjuvanted chimeric spike antigen boosts lung-resident memory T-cells and induces pan-sarbecovirus protective immunity
Claudio Counoupas[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Elizabeth Chan[SUP] #[/SUP][SUP] 1 2 3 [/SUP], Paco Pino[SUP] 4 [/SUP], Joshua Armitano[SUP] 4 [/SUP], Matt D Johansen[SUP] 5 [/SUP], Lachlan J Smith[SUP] 1 3 [/SUP], Caroline L Ashley[SUP] 1 3 [/SUP], Eva Estapé[SUP] 4 [/SUP], Jean Troyon[SUP] 4 [/SUP], Sibel Alca[SUP] 1 3 [/SUP], Stefan Miemczyk[SUP] 5 [/SUP], Nicole G Hansbro[SUP] 5 [/SUP], Gabriella Scandurra[SUP] 1 3 [/SUP], Warwick J Britton[SUP] 2 [/SUP], Thomas Courant[SUP] 6 [/SUP], Patrice M Dubois[SUP] 6 [/SUP], Nicolas Collin[SUP] 6 [/SUP], V Krishna Mohan[SUP] 7 [/SUP], Philip M Hansbro[SUP] 5 [/SUP], Maria J Wurm[SUP] 4 [/SUP], Florian M Wurm[SUP] 4 8 [/SUP], Megan Steain[SUP] 1 3 9 [/SUP], James A Triccas[SUP] 10 11 12 13 [/SUP]
Affiliations
- PMID: 40341541
- PMCID: PMC12062434
- DOI: 10.1038/s41541-025-01144-7
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.