Immunogenicity of prime-boost protein subunit vaccine strategies against SARS-CoV-2 in mice and macaques

• Published in: Nature communications Vol. 12; no. 1; pp. 1403 - 10
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03-03-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/31; 49; 59; 631/250/2152/1566; 631/250/2152/2153; 631/250/590; 631/326/596/4130; 64; 64/60; Animals; Antibodies; Antibodies, Neutralizing - immunology; Antibody Formation - physiology; Binding; Clinical trials; COVID-19 Vaccines - therapeutic use; Domains; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Homology; Humanities and Social Sciences; Humans; Immunogenicity; Macaca; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; multidisciplinary; Proteins; Receptors; SARS-CoV-2 - pathogenicity; Science; Science (multidisciplinary); Serology; Severe acute respiratory syndrome; Severe acute respiratory syndrome coronavirus 2; Spike protein; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; Vaccines; Viral Vaccines - therapeutic use
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-021-21665-8

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.
Current vaccine strategies for SARS-CoV-2 focus on eliciting neutralising antibodies to the spike protein (S), but differences in immunogenicity of full-length S versus receptor binding domain (RBD) only aren’t fully understood. Here, the authors show immunogenicity of different prime-boost strategies with S and/or RBD in mice and macaques.