[HTML][HTML] Neutralizing antibody vaccine for pandemic and pre-emergent coronaviruses

KO Saunders, E Lee, R Parks, DR Martinez, D Li… - Nature, 2021 - nature.com
KO Saunders, E Lee, R Parks, DR Martinez, D Li, H Chen, RJ Edwards, S Gobeil, M Barr…
Nature, 2021nature.com
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, 2, 3, 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 …
Abstract
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, 2, 3, 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.
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