Evaluation of the mRNA-1273 Vaccine against SARS-CoV-2 in Nonhuman Primates.N Engl J Med. 2020 10 15; 383(16):1544-1555.NEJM
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.
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.
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.
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.).
- Antibodies, Neutralizing
- Antibodies, Viral
- CD4 Antigens
- Coronavirus Infections
- Disease Models, Animal
- Dose-Response Relationship, Immunologic
- Immunization, Passive
- Macaca mulatta
- Pneumonia, Viral
- Spike Glycoprotein, Coronavirus
- Viral Load
- Viral Vaccines
- Virus Replication
- DNA vaccine protection against SARS-CoV-2 in rhesus macaques.
- ChAdOx1 nCoV-19 vaccine prevents SARS-CoV-2 pneumonia in rhesus macaques.
- A vaccine targeting the RBD of the S protein of SARS-CoV-2 induces protective immunity.
- Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: a preliminary report of a phase 1/2, single-blind, randomised controlled trial.
- SARS-CoV-2 infection protects against rechallenge in rhesus macaques.
- Development of an inactivated vaccine candidate for SARS-CoV-2.
- Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques.
- An Alphavirus-derived replicon RNA vaccine induces SARS-CoV-2 neutralizing antibody and T cell responses in mice and nonhuman primates.
- Isolation of potent SARS-CoV-2 neutralizing antibodies and protection from disease in a small animal model.
- Functional mapping of B-cell linear epitopes of SARS-CoV-2 in COVID-19 convalescent population.