A Newcastle disease virus-vector expressing a prefusion-stabilized spike protein of SARS-CoV-2 induces protective immune responses against prototype virus and variants of concern in mice and hamsters
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
Rapid development of coronavirus disease 2019 (COVID-19) vaccines and expedited authorization for use and approval has been proven beneficial to mitigate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spread and given hope in this desperate situation. It is believed that sufficient supplies and equitable allocations of vaccines are necessary to limit the global impact of the COVID-19 pandemic and the emergence of additional variants of concern. We have developed a COVID-19 vaccine based on Newcastle disease virus (NDV) that can be manufactured at high yields in embryonated eggs. Here we provide evidence that the NDV vector expressing an optimized spike antigen (NDV-HXP-S), upgraded from our previous construct, is a versatile vaccine that can be used live or inactivated to induce strong antibody responses and to also cross-neutralize variants of concern. The immunity conferred by NDV-HXP-S effectively counteracts SARS-CoV-2 infection in mice and hamsters. It is noteworthy that vaccine lots produced by existing egg-based influenza virus vaccine manufacturers in Vietnam, Thailand and Brazil exhibited excellent immunogenicity and efficacy in hamsters, demonstrating that NDV-HXP-S vaccines can be quickly produced at large-scale to meet global demands.
Article activity feed
-
SciScore for 10.1101/2021.07.06.451301: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Animal experiments: All the animal experiments were performed in accordance with protocols approved by the Icahn School of Medicine at Mount Sinai Institutional Animal Care and Use Committee (IACUC). Sex as a biological variable Mouse immunization and challenge studies: Female BALB/c mice were used in all studies. Randomization not detected. Blinding All sections were evaluated by a veterinary pathologist who was blinded to the vaccination groups in the Comparative Pathology Laboratory (CPL) at ISMMS. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources An HRP-conjugated goat anti-mouse IgA secondary antibody (PA1-74397 Invitrogen) was … SciScore for 10.1101/2021.07.06.451301: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Animal experiments: All the animal experiments were performed in accordance with protocols approved by the Icahn School of Medicine at Mount Sinai Institutional Animal Care and Use Committee (IACUC). Sex as a biological variable Mouse immunization and challenge studies: Female BALB/c mice were used in all studies. Randomization not detected. Blinding All sections were evaluated by a veterinary pathologist who was blinded to the vaccination groups in the Comparative Pathology Laboratory (CPL) at ISMMS. Power Analysis not detected. Cell Line Authentication not detected. Table 2: Resources
Antibodies Sentences Resources An HRP-conjugated goat anti-mouse IgA secondary antibody (PA1-74397 Invitrogen) was used at 1: 2000 dilution. anti-mouse IgAsuggested: (Thermo Fisher Scientific Cat# PA1-74397, RRID:AB_10985723)The plaques were immuno-stained with an anti-SARS-CoV-2 NP primary mouse monoclonal antibody 1C7C7 kindly provided by Dr. Thomas Moran at ISMMS. anti-SARS-CoV-2 NPsuggested: NoneAn HRP-conjugated goat anti-mouse secondary antibody was used at 1:2000 and the plaques were visualized using TrueBlue™ Peroxidase Substrate (SeraCare Life Sciences Inc.). anti-mousesuggested: NoneExperimental Models: Cell Lines Sentences Resources Viral titers in the lung homogenates were measured by plaque assay on Vero E6 cells. Vero E6suggested: RRID:CVCL_XD71)Experimental Models: Organisms/Strains Sentences Resources Mouse immunization and challenge studies: Female BALB/c mice were used in all studies. BALB/csuggested: RRID:IMSR_ORNL:BALB/cRl)Recombinant DNA Sentences Resources The sequence of the HXP-S was inserted into pNDV_LS/L289A rescue plasmid (between P and M genes) by in-Fusion cloning (Clontech). pNDV_LS/L289Asuggested: NoneThe recombination product was transformed into MAX Efficiency™ Stbl2™ Competent Cells (Thermo Fisher Scientific) to generate the pNDV-HXP-S rescue plasmid. pNDV-HXP-Ssuggested: NoneThe next day, cells were transfected with 2 μg of pNDV-HXP-S, 1 μg of pTM1-NP, 0.5 μg of pTM1-P, 0.5 μg of pTM1-L and 1 μg of pCI-T7opt were re-suspended in 250 μL of Opti-MEM (Gibco). pTM1-NPsuggested: NonepTM1-Psuggested: NonepTM1-Lsuggested: NonepCI-T7optsuggested: NoneSoftware and Algorithms Sentences Resources Statistical analysis: The statistical analysis was performed using GraphPad Prism 7.0. 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 NCT04764422 Recruiting Assess the Safety and Immunogenicity of NDV-HXP-S Vaccine in… NCT04830800 Recruiting A Phase 1/2 Safety and Immunogenicity Trial of COVID-19 Vacc… NCT04871737 Recruiting Study of a Live rNDV Based Vaccine Against COVID-19 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.
-