Safety and immunogenicity of a live recombinant Newcastle disease virus-based COVID-19 vaccine (Patria) administered via the intramuscular or intranasal route: Interim results of a non-randomized open label phase I trial in Mexico
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Abstract
There is still a need for safe, efficient and low-cost coronavirus disease 2019 (COVID-19) vaccines that can stop transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we evaluated a vaccine candidate based on a live recombinant Newcastle disease virus (NDV) that expresses a stable version of the spike protein in infected cells as well as on the surface of the viral particle (AVX/COVID-12-HEXAPRO, also known as NDV-HXP-S). This vaccine candidate can be grown in embryonated eggs at low cost similar to influenza virus vaccines and it can also be administered intranasally, potentially to induce mucosal immunity. We evaluated this vaccine candidate in prime-boost regimens via intramuscular, intranasal, or intranasal followed by intramuscular routes in an open label non-randomized non-placebo-controlled phase I clinical trial in Mexico in 91 volunteers. The primary objective of the trial was to assess vaccine safety and the secondary objective was to determine the immunogenicity of the different vaccine regimens. In the interim analysis reported here, the vaccine was found to be safe and the higher doses tested were found to be immunogenic when given intramuscularly or intranasally followed by intramuscular administration, providing the basis for further clinical development of the vaccine candidate. The study is registered under ClinicalTrials.gov identifier NCT04871737 . Funding was provided by Avimex and CONACYT.
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SciScore for 10.1101/2022.02.08.22270676: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: A written informed consent was obtained from each participant, as approved by COFEPRIS, to voluntarily participate in the study for 12 months including 11 visits to the site plus at least six telephone follow-up calls scheduled according to the date of the first visit. Sex as a biological variable Female and male participants between 18 and 55 years of age without prior immunity to SARS-CoV-2 were enrolled. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources However, a subsequent test of anti-spike antibodies, post-administration of the vaccine, showed a low, yet positive antibodies level (148.8 AU/mL anti-spikesuggest…SciScore for 10.1101/2022.02.08.22270676: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: A written informed consent was obtained from each participant, as approved by COFEPRIS, to voluntarily participate in the study for 12 months including 11 visits to the site plus at least six telephone follow-up calls scheduled according to the date of the first visit. Sex as a biological variable Female and male participants between 18 and 55 years of age without prior immunity to SARS-CoV-2 were enrolled. Randomization not detected. Blinding not detected. Power Analysis not detected. Table 2: Resources
Antibodies Sentences Resources However, a subsequent test of anti-spike antibodies, post-administration of the vaccine, showed a low, yet positive antibodies level (148.8 AU/mL anti-spikesuggested: NoneIn addition, the participants were subject to COVID-19 testing (nucleic acid-GeneFinder™ COVID-19 Plus RealAmpKit, and antibody-as above) to exclude prior or active infection, as such infection was part of the exclusion criteria. COVID-19 testing ( nucleic acid-GeneFinder™ COVID-19suggested: Noneantibody-assuggested: NoneDay 14, 21, 28, 42, 90, 180 and 365 visits include blood sampling for IgM – IgG – IgA antibodies, neutralizing antibodies, and T cell responses. IgM – IgG – IgAsuggested: NoneResults 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: We detected the following sentences addressing limitations in the study:Our study has several limitations. Quantitative neutralization assays with authentic SARS-CoV-2 could not be performed at the study site at the time of analysis due to biosafety restrictions. In addition, in this interim analysis, neutralizing activity against variants of concern could not be assessed. Furthermore, we were not able to directly compare immune responses induced by inactivated NDV-vectored SARS-CoV-2 vaccines (41) with those observed following administration of other authorized/licensed COVID-19 vaccines. We expect to perform these additional assays and direct comparisons at later time points as soon as reagents and materials become available. So far, the assessment of mucosal antibodies has also not been possible. Finally, this was a non-randomized open label study without a placebo control group, which is more prone to biases as compared to randomized and double-blinded study designs. In conclusion, we show that the live AVX/COVID-12-HEXAPRO vaccine has a safety profile that is remarkably independent of the dose and administration route with low frequency and intensity. Furthermore, the HD IM-IM and IN-IM vaccination regimens showed strong evidence of immunogenicity warranting further development of this vaccine candidate. Finally, it is important to note that the NDV vector technology is amenable to rapid changes in antigens expressed allowing for strain changes to match emerging viral variants. A B.1.1.529 (Omicron)-specific version of NDV-HXP-S is currently...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04871737 Active, not recruiting Study of a Live rNDV Based Vaccine Against COVID-19 NCT04830800 Recruiting A Phase 1/2 Safety and Immunogenicity Trial of COVID-19 Vacc… NCT04993209 Recruiting Clinical Trial of the COVID-19 Vaccine (Recombinant, Inactiv… NCT04764422 Recruiting Assess the Safety and Immunogenicity of NDV-HXP-S Vaccine in… 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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