Author: Tan, Hyon-Xhi; Juno, Jennifer A.; Lee, Wen Shi; Barber-Axthelm, Isaac; Kelly, Hannah G.; Wragg, Kathleen M.; Esterbauer, Robyn; Amarasena, Thakshila; Mordant, Francesca L.; Subbarao, Kanta; Kent, Stephen J.; Wheatley, Adam K.
Title: Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques Cord-id: 6pvnkug6 Document date: 2021_3_3
ID: 6pvnkug6
Snippet: SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogen
Document: SARS-CoV-2 vaccines are advancing into human clinical trials, with emphasis on eliciting high titres of neutralising antibodies against the viral spike (S). However, the merits of broadly targeting S versus focusing antibody onto the smaller receptor binding domain (RBD) are unclear. Here we assess prototypic S and RBD subunit vaccines in homologous or heterologous prime-boost regimens in mice and non-human primates. We find S is highly immunogenic in mice, while the comparatively poor immunogenicity of RBD is associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augments neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines are comparably immunogenic in macaques, eliciting serological neutralising activity that generally exceed levels in convalescent humans. These studies confirm recombinant S proteins as promising vaccine candidates and highlight multiple pathways to achieving potent serological neutralisation.
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