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Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques #MMPMID33658497
Tan HX; Juno JA; Lee WS; Barber-Axthelm I; Kelly HG; Wragg KM; Esterbauer R; Amarasena T; Mordant FL; Subbarao K; Kent SJ; Wheatley AK
Nat Commun 2021[Mar]; 12 (1): 1403 PMID33658497show ga
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.