Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses

• Published in: Nature (London) Vol. 594; no. 7864; pp. 553 - 559
• Main Authors: Saunders, Kevin O., Lee, Esther, Parks, Robert, Martinez, David R., Li, Dapeng, Chen, Haiyan, Edwards, Robert J., Gobeil, Sophie, Barr, Maggie, Mansouri, Katayoun, Alam, S. Munir, Sutherland, Laura L., Cai, Fangping, Sanzone, Aja M., Berry, Madison, Manne, Kartik, Bock, Kevin W., Minai, Mahnaz, Nagata, Bianca M., Kapingidza, Anyway B., Azoitei, Mihai, Tse, Longping V., Scobey, Trevor D., Spreng, Rachel L., Rountree, R. Wes, DeMarco, C. Todd, Denny, Thomas N., Woods, Christopher W., Petzold, Elizabeth W., Tang, Juanjie, Oguin, Thomas H., Sempowski, Gregory D., Gagne, Matthew, Douek, Daniel C., Tomai, Mark A., Fox, Christopher B., Seder, Robert, Wiehe, Kevin, Weissman, Drew, Pardi, Norbert, Golding, Hana, Khurana, Surender, Acharya, Priyamvada, Andersen, Hanne, Lewis, Mark G., Moore, Ian N., Montefiori, David C., Baric, Ralph S., Haynes, Barton F.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 24.06.2021; Nature Publishing Group
• Subjects: 631/250/255/2514; 631/250/590/2293; 631/250/590/2294; 631/326/596/4130; 82; 82/1; 82/51; 82/83; Adjuvants, Immunologic; Administration, Intranasal; Animals; Antibodies; Antibodies, Neutralizing - immunology; Betacoronavirus - immunology; Binding; Common Cold - immunology; Common Cold - prevention & control; Common Cold - virology; Control; Coronaviridae; Coronaviruses; COVID-19; COVID-19 - epidemiology; COVID-19 - immunology; COVID-19 - prevention & control; COVID-19 Vaccines - immunology; Cross Reactions - immunology; Dilution; Disease Models, Animal; Domains; Dosage and administration; Female; Health aspects; Humanities and Social Sciences; Humans; Immunization; Macaca - immunology; Male; Middle East respiratory syndrome; Models, Molecular; mRNA; multidisciplinary; Nanoparticles; Nanoparticles - chemistry; Neutralization; Neutralizing; Outbreaks; Pandemics; Receptors; Respiratory diseases; Respiratory tract; SARS-CoV-2 - immunology; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Spike Glycoprotein, Coronavirus - chemistry; Spike Glycoprotein, Coronavirus - immunology; Trachea; Vaccination; Vaccines; Viral antibodies; Viral diseases; Viral vaccines; Viral Vaccines - immunology; Viruses; United States; Middle East
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-021-03594-0

Betacoronaviruses caused the outbreaks of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome, as well as the current pandemic of SARS coronavirus 2 (SARS-CoV-2) 1 – 4 . Vaccines that elicit protective immunity against SARS-CoV-2 and betacoronaviruses that circulate in animals have the potential to prevent future pandemics. Here we show that the immunization of macaques with nanoparticles conjugated with the receptor-binding domain of SARS-CoV-2, and adjuvanted with 3M-052 and alum, elicits cross-neutralizing antibody responses against bat coronaviruses, SARS-CoV and SARS-CoV-2 (including the B.1.1.7, P.1 and B.1.351 variants). Vaccination of macaques with these nanoparticles resulted in a 50% inhibitory reciprocal serum dilution (ID 50 ) neutralization titre of 47,216 (geometric mean) for SARS-CoV-2, as well as in protection against SARS-CoV-2 in the upper and lower respiratory tracts. Nucleoside-modified mRNAs that encode a stabilized transmembrane spike or monomeric receptor-binding domain also induced cross-neutralizing antibody responses against SARS-CoV and bat coronaviruses, albeit at lower titres than achieved with the nanoparticles. These results demonstrate that current mRNA-based vaccines may provide some protection from future outbreaks of zoonotic betacoronaviruses, and provide a multimeric protein platform for the further development of vaccines against multiple (or all) betacoronaviruses. Immunization of macaques with nanoparticle-conjugated receptor-binding domain of SARS-CoV-2 adjuvanted with 3M-052 and alum results in cross-neutralizing antibodies against bat coronaviruses, SARS-CoV and SARS-CoV-2 variants, and may provide a platform for developing pan-coronavirus vaccines.