Evaluation of mRNA-1273 against SARS-CoV-2 B.1.351 Infection in Nonhuman Primates
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Abstract
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.
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SciScore for 10.1101/2021.05.21.445189: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Rhesus Macaque Model: Animal experiments were carried out in compliance with US National Institutes of Health regulations and approval from the Animal Care and Use Committee of the Vaccine Research Center and Bioqual, Inc. (Rockville, MD). Sex as a biological variable Male and female, 3-12 year-old Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Meso Scale ELISA for Mucosal Antibody Responses: Using previously described methods44, total S-specific IgG and IgA were determined by MULTI-ARRAY ELISA using Meso Scale technology (Meso Scale Discovery, MSD) total S-specific IgGsuggested: …SciScore for 10.1101/2021.05.21.445189: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Rhesus Macaque Model: Animal experiments were carried out in compliance with US National Institutes of Health regulations and approval from the Animal Care and Use Committee of the Vaccine Research Center and Bioqual, Inc. (Rockville, MD). Sex as a biological variable Male and female, 3-12 year-old Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Meso Scale ELISA for Mucosal Antibody Responses: Using previously described methods44, total S-specific IgG and IgA were determined by MULTI-ARRAY ELISA using Meso Scale technology (Meso Scale Discovery, MSD) total S-specific IgGsuggested: NoneExperimental Models: Cell Lines Sentences Resources 2 pseudotyped recombinant VSV-ΔG-firefly luciferase virus, BHK21/WI-2 cells (Kerafast, EH1011) were transfected with the Wuhan-1 strain (Genbank #: MN908947.3) S plasmid expressing full-length S with D614G mutation or S of B.1.351. BHK21/WI-2suggested: RRID:CVCL_HB78)Neutralization assays were completed on A549-ACE2-TMPRSS2 cells with serially diluted serum samples as previously described26. A549-ACE2-TMPRSS2suggested: NoneFocus Reduction Neutralization Test (FRNT): Viruses were propagated in Vero-TMPRSS2 cells to generate viral stocks. Vero-TMPRSS2suggested: JCRB Cat# JCRB1818, RRID:CVCL_YQ48)Viral titers were determined by focus-forming assay on VeroE6 cells. VeroE6suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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