Adenovirus type 5 SARS-CoV-2 vaccines delivered orally or intranasally reduced disease severity and transmission in a hamster model
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (ScreenIT)
Abstract
Transmission-blocking strategies that slow the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and protect against coronavirus disease 2019 (COVID-19) are needed. We have developed an orally delivered adenovirus type 5–vectored SARS-CoV-2 vaccine candidate that expresses the spike protein. Here, we demonstrated that hamsters vaccinated by the oral or intranasal route had robust and cross-reactive antibody responses. We then induced a postvaccination infection by inoculating vaccinated hamsters with SARS-CoV-2. Orally or intranasally vaccinated hamsters had decreased viral RNA and infectious virus in the nose and lungs and experienced less lung pathology compared to mock-vaccinated hamsters after SARS-CoV-2 challenge. Naïve hamsters exposed in a unidirectional air flow chamber to mucosally vaccinated, SARS-CoV-2–infected hamsters also had lower nasal swab viral RNA and exhibited fewer clinical symptoms than control animals, suggesting that the mucosal route reduced viral transmission. The same platform encoding the SARS-CoV-2 spike and nucleocapsid proteins elicited mucosal cross-reactive SARS-CoV-2–specific IgA responses in a phase 1 clinical trial (NCT04563702). Our data demonstrate that mucosal immunization is a viable strategy to decrease SARS-CoV-2 disease and airborne transmission.
Article activity feed
-
-
SciScore for 10.1101/2021.10.03.462919: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Animal work was performed at Lovelace Biomedical, with approval from the Institutional Animal Care and Use Committee. 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 Following 2-hr sample incubation, the plate was washed and SULFO-TAG (MSD) anti-hamster IgA (Brookwood Biomedical) detection antibody was added. anti-hamster IgAsuggested: NoneExperimental Models: Cell Lines Sentences Resources VeroE6 cell monolayers at ≥ 90% confluency in 96-well plates were rinsed with PBS. VeroE6suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)Recombinant DNA Senten… SciScore for 10.1101/2021.10.03.462919: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics IACUC: Animal work was performed at Lovelace Biomedical, with approval from the Institutional Animal Care and Use Committee. 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 Following 2-hr sample incubation, the plate was washed and SULFO-TAG (MSD) anti-hamster IgA (Brookwood Biomedical) detection antibody was added. anti-hamster IgAsuggested: NoneExperimental Models: Cell Lines Sentences Resources VeroE6 cell monolayers at ≥ 90% confluency in 96-well plates were rinsed with PBS. VeroE6suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)Recombinant DNA Sentences Resources Vaccine constructs: r-Ad-S is a rAd5 vector containing full-length SARS-CoV-2 S gene under control of the CMV promoter. rAd5suggested: NoneSoftware and Algorithms Sentences Resources IgA MSD: S1 protein was biotinylated according to manufacturer’s instructions (EZ-link, Thermofisher), and was conjugated to a U-Plex MSD linker (Mesoscale Diagnostics). Thermofishersuggested: (ThermoFisher; SL 8; Centrifuge, RRID:SCR_020809)Results from OddPub: Thank you for sharing your data.
Results from LimitationRecognizer: We detected the following sentences addressing limitations in the study:Our study does have limitations. Firstly, we do not measure mucosal T cell responses which are shown to play a role in limiting SARS-CoV-2 infection at mucosal sites19. Additionally, the SAR-CoV-2 challenge dose we used was above physiological dose likely to be picked up by an environmental exposure, as evidenced by the high viral RNA load in the nose at 1-day post infection in all index hamsters. It is likely that mucosal immunization would provide greater protection against SARS-CoV-2 transmission when lower doses of challenge virus are used. Our study was meant to be a stringent challenge to clearly identify advantages between vaccine groups. For practical reasons, such as the limitation of the number of aerosol transmission chambers, lower dose levels or evaluation at later time points were not done. Additionally, future work should include challenging mucosally-vaccinated hamsters with the Delta variant and other variants of concern. An orally-delivered, temperature-stable SARS-CoV-2 vaccine is ideal for global vaccination, where adequate storage and qualified health care providers maybe in short supply. IN delivery has some of the same advantages, but translating IN SARS-CoV-2 vaccination efficacy in humans has proven to be more difficult than in animals20,21. Implementing oral vaccine campaigns around the world has been done, as evidenced by the rotavirus and poliovirus vaccination efforts22,23. We have previously demonstrated that our SARS-CoV-2 clinical candidate vac...
Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04563702 Active, not recruiting Safety and Immunogenicity Trial of an Oral SARS-CoV-2 Vaccin… 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.
-
