Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates.
Level 5 - mechanism / opinion, no new human data
Preclinical animal study (nonhuman primates)
PubMed 32722908 · doi:10.1056/NEJMoa2024671
What was done
Nonhuman primates received 10 μg or 100 μg of mRNA-1273 (encoding the prefusion-stabilized spike protein of SARS-CoV-2) or no vaccine. Antibody and T-cell responses were evaluated prior to upper- and lower-airway challenge with SARS-CoV-2. Viral replication and viral genomes were measured by PCR in bronchoalveolar-lavage fluid and nasal swabs, and lung tissue underwent histopathological examination and viral quantification.
What was found
mRNA-1273 elicited live-virus reciprocal 50% inhibitory dilution geometric mean titers of 501 in the 10-μg dose group and 3,481 in the 100-μg dose group, exceeding human convalescent serum titers. Responses were Th1-biased CD4 T-cell responses with low or undetectable Th2 or CD8 T-cell responses. By day 2 post-challenge, viral replication in bronchoalveolar-lavage fluid was undetectable in 7 of 8 animals in each vaccinated group. In nasal swabs, viral replication was undetectable in all 8 animals in the 100-μg group by day 2. Limited lung inflammation and detectable viral genome or antigen were observed in vaccinated animals.
Why it matters
These data provided preclinical proof-of-concept in nonhuman primates that mRNA-1273 protects against SARS-CoV-2 replication in both upper and lower airways without inducing immunopathology.
Limits
The study was conducted in nonhuman primates rather than humans, total group sizes are small (n = 8 per evaluated cohort), and long-term durability of immune protection was not reported in the abstract.
Cited by
- supports Animals in preclinical animal safety and efficacy trials for COVID-19 vaccines did not die, allowing the trials to advance to human phases.