Use of eVLP-based vaccine candidates to broaden immunity against SARS-CoV-2 variants
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Abstract
Rapid emergence of SARS-CoV-2 variants is a constant threat and a major hurdle to reach heard immunity. We produced VBI-2905a, an enveloped virus-like particle (eVLP)-based vaccine candidate expressing prefusion spike protein from the Beta variant that contains several escape mutations. VBI-2905a protected hamsters against infection with a Beta variant virus and induced high levels of neutralizing antibodies against Beta RBD. In a heterologous vaccination regimen, a single injection of VBI-2905a in animals previously immunized with VBI-2902, a vaccine candidate expressing S from ancestral SARS-CoV-2, hamsters were equally protected against Beta variant infection. As an alternate strategy to broaden immunity, we produced a trivalent vaccine expressing the prefusion spike protein from SARS-CoV-2 together with unmodifed S from SARS-CoV-1 and MERS-CoV. Relative to immunity induced against the ancestral strain, the trivalent vaccine VBI-2901a induced higher and more consistent antibody binding and neutralizing responses against a panel of variants including Beta, Delta, Kappa, and Lambda, with evidence for broadening of immunity rather than just boosting cross-reactive antibodies.
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SciScore for 10.1101/2021.09.28.462109: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: The animal studies were conducted under ethics protocols approved by the NRC Animal Care Committee.
IACUC: The animal studies were conducted under ethics protocols approved by the NRC Animal Care Committee.
IRB: The study was conducted under approval of the CCAC committee at the Vaccine and Infectious Disease Organization (VIDO) International Vaccine Centre (Saskatchewan, Canada).Sex as a biological variable Mouse immunization study: Six- to 8-week-old female C57BL/6 mice were purchased from Charles River (St Constant, Quebec Canada). Randomization Mice were randomly assigned to experimental groups of 10 to 15 mice and received intraperitoneal (IP) injections with 0.5 mL of … SciScore for 10.1101/2021.09.28.462109: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Field Sample Permit: The animal studies were conducted under ethics protocols approved by the NRC Animal Care Committee.
IACUC: The animal studies were conducted under ethics protocols approved by the NRC Animal Care Committee.
IRB: The study was conducted under approval of the CCAC committee at the Vaccine and Infectious Disease Organization (VIDO) International Vaccine Centre (Saskatchewan, Canada).Sex as a biological variable Mouse immunization study: Six- to 8-week-old female C57BL/6 mice were purchased from Charles River (St Constant, Quebec Canada). Randomization Mice were randomly assigned to experimental groups of 10 to 15 mice and received intraperitoneal (IP) injections with 0.5 mL of adjuvanted SARS-CoV-2 eVLPs as described elsewhere (Fluckiger, 2021). Blinding not detected. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources Antibody binding titers: Anti-SARS-CoV-2 specific IgG binding titers in sera were measured by standard ELISA procedure described elsewhere (Kirchmeier et al., 2014), using recombinant SARS-CoV-2 S RBD proteins (Sinobiological). Anti-SARS-CoV-2suggested: NoneExperimental Models: Cell Lines Sentences Resources Virus neutralization assays: Neutralizing activity in mouse serum samples was measured by standard plaque reduction neutralization test (PRNT) on Vero cells at the NRC using 100 PFU of SARS-CoV-2/Canada/ON/VIDO-01/2020 (Wu-1 virus) or hCoV-19/South Africa/KRISP-EC-K005321/2020 (Beta virus). Verosuggested: NoneLuciferase activity in infected hACE2-HEK293 cells was measured with a Bright-Glo Luciferase assay system (Promega) and a Beckman Coulter DTX880 plate reader. hACE2-HEK293suggested: NoneExperimental Models: Organisms/Strains Sentences Resources Mouse immunization study: Six- to 8-week-old female C57BL/6 mice were purchased from Charles River (St Constant, Quebec Canada). C57BL/6suggested: NoneRecombinant DNA Sentences Resources We produced infectious SARS-CoV-2pp carrying a GFP-firefly luciferase double reporter gene (plasmid pjm155, Garrone et al., 2011) instead of green fluorescent protein (GFP). pjm155suggested: NoneSoftware and Algorithms Sentences Resources Expression of SARS-CoV-2 S, SARS-CoV-1 S, MERS-CoV S and GAG were determined by Western blot analysis (Supplementary material Fig.S1). GAGsuggested: NoneStatistics: All statistical analyses were performed using GraphPad Prism 9 software (La Jolla, CA). GraphPad Prismsuggested: (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: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04773665 Active, not recruiting Safety, Tolerability, and Immunogenicity of the COVID-19 Vac… 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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