A novel chimeric coronavirus spike vaccine combining SARS-CoV-2 RBD and scaffold domains from HKU-1 elicits potent neutralising antibody responses
- Author(s)
- Zoest, VP; Lee, WS; Murdiyarso, L; Burmas, L; Pymm, P; Esterbauer, R; Kelly, A; Kelly, HG; Barber-Axthelm, I; Cooney, JP; Davidson, KC; Dayton, M; McAleese, CE; Gillard, M; Hughes, K; Jones, ML; Pellegrini, M; Tham, WH; Hughes, B; Kent, SJ; Wheatley, AK; Juno, JA; Tan, HX;
- Journal Title
- NPJ Vaccines
- Publication Type
- Nov 28
- Abstract
- The SARS-CoV-2 spike receptor binding domain (RBD) is the major target for neutralising antibodies. However, subdomains like RBD may constrain the availability of CD4 T follicular helper (TFH) cells and impact immunogenicity. We engineered a chimeric trimeric RBD (CTR) glycoprotein, replacing the RBD of HKU-1 spike with SARS-CoV-2 RBD (ancestral WT/Omicron BA.2). This maintains trimerised RBD, while providing CD4 help via the HKU-1 scaffold. In C57BL/6 mice, CTR-BA.2 elicited high anti-BA.2-RBD IgG and neutralising titres, matching native spike responses. Germinal centre B cells were predominantly WT(+)/BA.2(+) cross-reactive, and TFH predominantly recognised HKU-1 epitopes, demonstrating scaffold-directed help. In macaques, CTR-WT elicited comparable anti-RBD IgG, anti-spike IgG and neutralising responses to native spike, with elevated RBD-specific GC B cells in draining lymph nodes. Macaque TFH responses targeted RBD, NTD/S2 or HKU-1 peptides. This chimeric design overcomes poor RBD immunogenicity by engaging CD4 TFH, maintaining neutralising responses that is non-inferior to native spike.
- Publisher
- Springer Nature
- Research Division(s)
- Infection and Global Health
- PubMed ID
- 41315254
- Publisher's Version
- https://doi.org/10.1038/s41541-025-01323-6
- Open Access at Publisher's Site
https://doi.org/10.1038/s41541-025-01323-6- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-12-02 09:39:28
Last Modified: 2025-12-02 09:40:42