mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants
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Abstract
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the causative infection of a global pandemic that has led to more than 2 million deaths worldwide. The Moderna mRNA-1273 vaccine has demonstrated ~94% efficacy in a Phase 3 study and has been approved under Emergency Use Authorization. The emergence of SARS-CoV-2 variants with mutations in the spike protein, most recently circulating isolates from the United Kingdom (B.1.1.7) and Republic of South Africa (B.1.351), has led to lower neutralization from convalescent serum by pseudovirus neutralization (PsVN) assays and resistance to certain monoclonal antibodies. Here, using two orthogonal VSV and lentivirus PsVN assays expressing spike variants of 20E (EU1), 20A.EU2, D614G-N439, mink cluster 5, B.1.1.7, and B.1.351 variants, we assessed the neutralizing capacity of sera from human subjects or non-human primates (NHPs) that received mRNA-1273. No significant impact on neutralization against the B.1.1.7 variant was detected in either case, however reduced neutralization was measured against the mutations present in B.1.351. Geometric mean titer (GMT) of human sera from clinical trial participants in VSV PsVN assay using D614G spike was 1/1852. VSV pseudoviruses with spike containing K417N-E484K-N501Y-D614G and full B.1.351 mutations resulted in 2.7 and 6.4-fold GMT reduction, respectively, when compared to the D614G VSV pseudovirus. Importantly, the VSV PsVN GMT of these human sera to the full B.1.351 spike variant was still 1/290, with all evaluated sera able to fully neutralize. Similarly, sera from NHPs immunized with 30 or 100μg of mRNA-1273 had VSV PsVN GMTs of ~ 1/323 or 1/404, respectively, against the full B.1.351 spike variant with a ~ 5 to 10-fold reduction compared to D614G. Individual mutations that are characteristic of the B.1.1.7 and B.1.351 variants had a similar impact on neutralization when tested in VSV or in lentivirus PsVN assays. Despite the observed decreases, the GMT of VSV PsVN titers in human vaccinee sera against the B.1.351 variant remained at ~1/300. Taken together these data demonstrate reduced but still significant neutralization against the full B.1.351 variant following mRNA-1273 vaccination.
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SciScore for 10.1101/2021.01.25.427948: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Animal Studies: Experiments in animals were performed in compliance with National Institutes of Health (NIH) regulations and with approval from the Animal Care and Use Committee of the Vaccine Research Center. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Female and male Indian-origin rhesus macaques (12 of each sex; age range, 3 to 6 years) were sorted according to sex, age, and weight, and then stratified into groups. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources To make SARS-CoV-2 full-length spike pseudotyped recombinant VSV-ΔG-firefly … SciScore for 10.1101/2021.01.25.427948: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: Animal Studies: Experiments in animals were performed in compliance with National Institutes of Health (NIH) regulations and with approval from the Animal Care and Use Committee of the Vaccine Research Center. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Female and male Indian-origin rhesus macaques (12 of each sex; age range, 3 to 6 years) were sorted according to sex, age, and weight, and then stratified into groups. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources To make SARS-CoV-2 full-length spike pseudotyped recombinant VSV-ΔG-firefly luciferase virus, BHK-21/WI-2 cells (Kerafast, EH1011) were transfected with the spike expression plasmid and subsequently infected with VSVΔG-firefly-luciferase as previously described (Whitt, 2010). BHK-21/WI-2suggested: RRID:CVCL_HB78)The virus-serum mix was subsequently used to infect A549-hACE2-TMPRSS2 cells for 18 hr at 37 Celsius before adding ONE-Glo reagent (Promega E6120) for measurement of luciferase signal (relative luminescence unit; RLU). A549-hACE2-TMPRSS2suggested: NoneSoftware and Algorithms Sentences Resources IC50 titers were determined using a log(agonist) vs. normalized-response (variable slope) nonlinear regression model in Prism v8 (GraphPad) GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)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 scite Reference Check: We found no unreliable references.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.
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SciScore for 10.1101/2021.01.25.427948: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement DISCUSSION We assessed the neutralization capacity of sera from eight phase 1 clinical trial participants (aged 18-55 years) who received two 100 µg doses of mRNA-1273, and NHPs immunized with two doses of 30 µg or 100 µg of mRNA-1273. METHODS Animal Studies Experiments in animals were performed in compliance with National Institutes of Health (NIH) regulations and with approval from the Animal Care and Use Committee of the Vaccine Research Center. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Female and male Indian-origin rhesus macaques (12 of each sex; age range, 3 to 6 years) were sorted according to sex, … SciScore for 10.1101/2021.01.25.427948: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement DISCUSSION We assessed the neutralization capacity of sera from eight phase 1 clinical trial participants (aged 18-55 years) who received two 100 µg doses of mRNA-1273, and NHPs immunized with two doses of 30 µg or 100 µg of mRNA-1273. METHODS Animal Studies Experiments in animals were performed in compliance with National Institutes of Health (NIH) regulations and with approval from the Animal Care and Use Committee of the Vaccine Research Center. Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Female and male Indian-origin rhesus macaques (12 of each sex; age range, 3 to 6 years) were sorted according to sex, age, and weight, and then stratified into groups. Cell Line Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources To make SARS-CoV-2 full-length spike pseudotyped recombinant VSV-ΔG-firefly luciferase virus, BHK21/WI-2 cells (Kerafast, EH1011) were transfected with the spike expression plasmid and subsequently infected with VSV∆G-firefly-luciferase as previously described (Whitt, 2010). BHK21/WI-2suggested: RRID:CVCL_HB78)The virus-serum mix was subsequently used to infect A549-hACE2TMPRSS2 cells for 18 hr at 37 Celsius before adding ONE-Glo reagent (Promega E6120) for measurement of luciferase signal (relative luminescence unit; RLU). A549-hACE2TMPRSS2suggested: NoneSoftware and Algorithms Sentences Resources IC50 titers were determined using a log(agonist) vs. normalized-response (variable slope) nonlinear regression model in Prism v8 (GraphPad) GraphPadsuggested: (GraphPad Prism, RRID:SCR_002798)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.
About SciScore
SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.
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