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Protocol for Recombinant RBD-based SARS Vaccines: Protein Preparation, Animal Vaccination and Neutralization Detection
Published on: May 2, 2011
mRNA-1273 protects against SARS-CoV-2 beta infection in nonhuman primates
Kizzmekia S Corbett1,2, Anne P Werner1, Sarah O' Connell1
1Vaccine Research Center; National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Abstract:
B.1.351 is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant most resistant to antibody neutralization. We demonstrate how the dose and number of immunizations influence protection. Nonhuman primates received two doses of 30 or 100 µg of Moderna's mRNA-1273 vaccine, a single immunization of 30 µg, or no vaccine. Two doses of 100 µg of mRNA-1273 induced 50% inhibitory reciprocal serum dilution neutralizing antibody titers against live SARS-CoV-2 p.Asp614Gly and B.1.351 of 3,300 and 240, respectively. Higher neutralizing responses against B.1.617.2 were also observed after two doses compared to a single dose. After challenge with B.1.351, there was ~4- to 5-log10 reduction of viral subgenomic RNA and low to undetectable replication in bronchoalveolar lavages in the two-dose vaccine groups, with a 1-log10 reduction in nasal swabs in the 100-µg group. These data establish that a two-dose regimen of mRNA-1273 will be critical for providing upper and lower airway protection against major variants of concern.
Insights
Two doses of the mRNA-1273 vaccine provide critical protection against SARS-CoV-2 variants. This immunization strategy is essential for upper and lower airway defense against concerning strains.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- The B.1.351 variant of SARS-CoV-2 exhibits significant resistance to antibody neutralization.
- Understanding the impact of vaccine dosage and immunization schedules is crucial for effective protection.
Purpose of the Study:
- To evaluate the influence of dose and number of immunizations with Moderna's mRNA-1273 vaccine on protection against SARS-CoV-2 variants.
- To assess the neutralizing antibody titers and in vivo protection conferred by different mRNA-1273 vaccination regimens.
Main Methods:
- Nonhuman primates were administered varying doses (30 or 100 µg) and numbers (single or two doses) of mRNA-1273 vaccine or received no vaccine.
- Serum samples were analyzed for neutralizing antibody titers against live SARS-CoV-2 strains, including B.1.351.
- Following challenge with the B.1.351 variant, viral load in respiratory tracts was quantified.
Main Results:
- Two 100 µg doses of mRNA-1273 induced high neutralizing antibody titers against SARS-CoV-2 strains, including B.1.351.
- Two-dose regimens elicited superior neutralizing responses compared to single doses, particularly against variants like B.1.617.2.
- Vaccinated nonhuman primates showed significant reductions in viral RNA and replication after B.1.351 challenge, especially in the two-dose groups.
Conclusions:
- A two-dose regimen of mRNA-1273 is critical for robust protection against SARS-CoV-2 variants.
- The vaccine's efficacy extends to both upper and lower airway protection.
- Vaccine dose and schedule significantly influence the level of protection achieved against resistant SARS-CoV-2 strains.
