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Published on: May 2, 2011
Evaluation of mRNA-1273 against SARS-CoV-2 B.1.351 Infection in Nonhuman Primates
Background:
Vaccine efficacy against the B.1.351 variant following mRNA-1273 vaccination in humans has not been determined. Nonhuman primates (NHP) are a useful model for demonstrating whether mRNA-1273 mediates protection against B.1.351.
Methods:
Nonhuman primates received 30 or 100 µg of mRNA-1273 as a prime-boost vaccine at 0 and 4 weeks, a single immunization of 30 µg at week 0, or no vaccine. Antibody and T cell responses were assessed in blood, bronchioalveolar lavages (BAL), and nasal washes. Viral replication in BAL and nasal swabs were determined by qRT-PCR for sgRNA, and histopathology and viral antigen quantification were performed on lung tissue post-challenge.
Results:
Eight weeks post-boost, 100 µg x2 of mRNA-1273 induced reciprocal ID 50 neutralizing geometric mean titers against live SARS-CoV-2 D614G and B.1.351 of 3300 and 240, respectively, and 430 and 84 for the 30 µg x2 group. There were no detectable neutralizing antibodies against B.1351 after the single immunization of 30 µg. On day 2 following B.1.351 challenge, sgRNA in BAL was undetectable in 6 of 8 NHP that received 100 µg x2 of mRNA-1273, and there was a ∼2-log reduction in sgRNA in NHP that received two doses of 30 µg compared to controls. In nasal swabs, there was a 1-log 10 reduction observed in the 100 µg x2 group. There was limited inflammation or viral antigen in lungs of vaccinated NHP post-challenge.
Conclusions:
Immunization with two doses of mRNA-1273 achieves effective immunity that rapidly controls lower and upper airway viral replication against the B.1.351 variant in NHP.
Insights
Two doses of mRNA-1273 vaccine effectively protect nonhuman primates against the B.1.351 variant. The vaccine rapidly controls viral replication in both upper and lower airways, demonstrating its efficacy against this SARS-CoV-2 strain.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Human vaccine efficacy against the B.1.351 SARS-CoV-2 variant remains undetermined.
- Nonhuman primates (NHP) serve as a relevant model to assess mRNA-1273 vaccine protection against B.1.351.
Approach:
- NHP received mRNA-1273 (30 or 100 µg) as prime-boost, single dose, or no vaccine.
- Antibody and T cell responses were measured in blood, bronchioalveolar lavages (BAL), and nasal washes.
- Viral replication in BAL and nasal swabs was quantified by qRT-PCR for sgRNA; lung tissue was analyzed for histopathology and viral antigen.
Key Points:
- Two mRNA-1273 doses induced neutralizing antibodies against B.1.351, with higher titers for the 100 µg dose.
- Viral replication (sgRNA) in BAL was undetectable in 6/8 NHP receiving 100 µg x2 mRNA-1273 post-B.1.351 challenge.
- Reduced viral replication and limited lung inflammation were observed in vaccinated NHP.
Conclusions:
- Two doses of mRNA-1273 confer effective immunity against the B.1.351 variant in NHP.
- The vaccine rapidly controls viral replication in both lower and upper airways.
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