Prime-boost protein subunit vaccines against SARS-CoV-2 are highly immunogenic in mice and macaques

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

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 assessed 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 was associated with limiting germinal centre and T follicular helper cell activity. Boosting S-primed mice with either S or RBD significantly augmented neutralising titres, with RBD-focussing driving moderate improvement in serum neutralisation. In contrast, both S and RBD vaccines were 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.