Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates

By Kizzmekia S. Corbett, Barbara Flynn, K. Foulds, J. Francica, Seyhan Boyoglu-Barnum, Anne P. Werner, B. Flach, S. O'connell, Kevin W. Bock, Mahnaz Minai and 64 more. New England Journal of Medicine, 2020

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Abstract Background Vaccines to prevent coronavirus disease 2019 (Covid-19) are urgently needed. The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines on viral replication in both upper and lower airways is important to evaluate in nonhuman primates. Methods Nonhuman primates received 10 or 100 μg of mRNA-1273, a vaccine encoding the prefusion-stabilized spike protein of SARS-CoV-2, or no vaccine. Antibody and T-cell responses were assessed before upper- and lower-airway challenge with SARS-CoV-2. Active viral replication and viral genomes in bronchoalveolar-lavage (BAL) fluid and nasal swab specimens were assessed by polymerase chain reaction, and histopathological analysis and viral quantification were performed on lung-tissue specimens. Results The mRNA-1273 vaccine candidate induced antibody levels exceeding those in human convalescent-phase serum, with live-virus reciprocal 50% inhibitory dilution (ID50) geometric mean titers of 501 in the 10-μg dose group and 3481 in the 100-μg dose group. Vaccination induced type 1 helper T-cell (Th1)–biased CD4 T-cell responses and low or undetectable Th2 or CD8 T-cell responses. Viral replication was not detectable in BAL fluid by day 2 after challenge in seven of eight animals in both vaccinated groups. No viral replication was detectable in the nose of any of the eight animals in the 100-μg dose group by day 2 after challenge, and limited inflammation or detectable viral genome or antigen was noted in lungs of animals in either vaccine group. Conclusions Vaccination of nonhuman primates with mRNA-1273 induced robust SARS-CoV-2 neutralizing activity, rapid protection in the upper and lower airways, and no pathologic changes in the lung. (Funded by the National Institutes of Health and others.)

Subfields: Infectious Diseases, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/3421beb461a9e3e12e970ccbac7a0cfc2e738da8

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Citations in the corpus

mRNA-based therapeutics: powerful and versatile tools to combat diseases (2022, methodology): “lungs of mice and rhesus macaques challenged with SARS-CoV-2 and evoked a Th1-biased immune response in healthy adults (NCT04283461, NCT04470427).(333) An mRNA vaccine (CV7201) was developed by using mRNA encoding the glycoprotein of rabies virus to treat rabies, which showed temperature stability a”
Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity (2020, neutral): “, 2020), with additional interest in elicitation of CD4 or CD8 T cells (Corbett et al., 2020; Folegatti et al., 2020; Jackson et al., 2020; Mercado et al., 2020; Sahin et al., 2020).”
mRNA Vaccines in the COVID-19 Pandemic and Beyond. (2021, methodology): “The vaccine was evaluated in animals in parallel with phase I clinical testing (18, 19).”
Animal models for COVID-19 (2020, background): “Recent studies have reported the immunogenicity and protective efficacy of several candidates for a COVID-19 vaccine in the rhesus macaque model 57–61 .”
Immunological memory to SARS-CoV-2 assessed for up to 8 months after infection (2021, background): “Immunization studies in nonhuman primates have indicated that circulating neutralization titers of ~200 may provide sterilizing immunity against a relatively high-dose URT challenge (66), and neutralizing titers of ~3400 may provide sterilizing immunity against a very high doseURT challenge (67), al”