Immunogenicity and In vivo protection of a variant nanoparticle vaccine that confers broad protection against emerging SARS-CoV-2 variants
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Abstract
The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) continues to spread globally. As SARS-CoV-2 has transmitted from person to person, variant viruses have emerged with elevated transmission rates and higher risk of infection for vaccinees. We present data showing that a recombinant prefusion-stabilized Spike (rS) protein based on the B.1.351 sequence (rS-B.1.351) was highly immunogenic in mice and produced neutralizing antibodies against SARS-CoV-2/WA1, B.1.1.7, and B.1.351. Mice vaccinated with our prototype vaccine NVX-CoV2373 (rS-WU1) or rS-B.1.351 alone, in combination, or as a heterologous prime boost, were protected when challenged with live SARS-CoV-2/B.1.1.7 or SARS-CoV-2/B.1.351. Virus titer was reduced to undetectable levels in the lungs post-challenge in all vaccinated mice, and Th1-skewed cellular responses were observed. A strong anamnestic response was demonstrated in baboons boosted with rS-B.1.351 approximately one year after immunization with NVX-CoV2373 (rS-WU1). An rS-B.1.351 vaccine alone or in combination with prototype rS-WU1 induced protective antibody- and cell-mediated responses that were protective against challenge with SARS-CoV-2 variant viruses.
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SciScore for 10.1101/2021.06.08.447631: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources 1.351 in plates that were pre-coated with anti-IFN-γ or anti-IL-5 antibodies. anti-IFN-γsuggested: Noneanti-IL-5suggested: NoneExperimental Models: Cell Lines Sentences Resources Titer of stock was determined by plaque assay using Vero E6 cells as described previously(21). Vero E6suggested: RRID:CVCL_XD71)Recombinant DNA Sentences Resources Briefly, 4 × 105 splenocytes in a volume of 200⍰µL were stimulated with rS-WU1 or rS-B. rS-WU1suggested: NoneSoftware and Algorithms Sentences Resources Briefl… SciScore for 10.1101/2021.06.08.447631: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics not detected. Sex as a biological variable not detected. Randomization not detected. Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources 1.351 in plates that were pre-coated with anti-IFN-γ or anti-IL-5 antibodies. anti-IFN-γsuggested: Noneanti-IL-5suggested: NoneExperimental Models: Cell Lines Sentences Resources Titer of stock was determined by plaque assay using Vero E6 cells as described previously(21). Vero E6suggested: RRID:CVCL_XD71)Recombinant DNA Sentences Resources Briefly, 4 × 105 splenocytes in a volume of 200⍰µL were stimulated with rS-WU1 or rS-B. rS-WU1suggested: NoneSoftware and Algorithms Sentences Resources Briefly, Vero E6 cells (ATCC# CRL 1586) were cultured in DMEM (Quality Biological), supplemented with 10% (v/v Quality Biologicalsuggested: NoneData was analyzed in Prism 9 (Graphpad). Graphpadsuggested: (GraphPad, RRID:SCR_000306)A 4-parameter logistic curve was fit to these neutralization data in PRISM (GraphPad, San Diego, CA) and the dilution required to neutralize 50% of the virus (PRNT50) was calculated based on that curve fit. PRISMsuggested: (PRISM, RRID:SCR_005375)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.
- No funding statement was detected.
- No protocol registration statement was detected.
Results from scite Reference Check: We found no unreliable references.
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