SARS-CoV-2 oral tablet vaccination induces neutralizing mucosal IgA in a phase 1 open label trial

Background Despite the plethora of efficacious vaccines to the initial Wuhan strain of SARS-CoV-2, these do not induce robust mucosal immunity, offering limited protection against breakthrough infection and replication in the respiratory tract. The mucosa is the first line of defense, therefore a vaccine that induces a mucosal IgA response could be an important strategy in curbing the global pandemic. Methods We conducted a single-site, dose-ranging, open-label clinical trial of an oral SARS-CoV-2 vaccine to determine safety and immunogenicity. This tablet vaccine is comprised of a non-replicating adenoviral vector expressing the SARS-CoV-2 Spike and Nucleocapsid genes and a double-stranded RNA adjuvant. 35 adult subjects meeting inclusion/exclusion criteria received a single low (1×1010 IU) or high (5×1010 IU) dose and 5 subjects received two low doses. Nasal, saliva and serum samples were assessed for the presence of IgA, IgG and surrogate neutralizing antibodies. Convalescent subjects between 1-8 months post infection were recruited to give nasal, saliva, and serum samples for comparison. Results The vaccine was well tolerated without any dose-limiting toxicity observed. No serum neutralizing antibodies were observed, but modest IgA responses were seen in serum post immunization. The majority of vaccine recipients had an increase in mucosal secretory IgA which was highly cross-reactive against all coronaviruses tested and persisted up to 360 days. Furthermore, the nasal IgA induced by vaccination has superior neutralizing activity compared to convalescent nasal samples. Conclusion The vaccine was safe, well tolerated and generated mucosal immune responses including cross-reactive surrogate neutralizing secretory IgA. These results demonstrate the ability of a mucosal vaccine to induce long-lasting mucosal IgA to SARS-CoV-2. ![Figure][1] ### Competing Interest Statement All authors are employees of Vaxart, Inc., and have received stock options and compensation as part of their employment. ### Clinical Trial NCT04563702 ### Funding Statement This study did not receive any external funding ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was conducted in accordance with applicable Good Clinical Practice guidelines, the United States Code of Federal Regulations, and the International Conference on Harmonization guidelines. IRB approval was obtained from Aspire IRB (Seattle/WA; AAHRPP accredited) before study specific screening and enrollment of subjects. Informed consent was obtained from all subjects after discussion of the study procedures and potential risks. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript [1]: pending:yes