Phase I study of a SARS-CoV-2 mRNA vaccine PTX-COVID19-B

PTX-COVID19-B mRNA vaccine encodes for SARS-CoV-2 Spike protein G614 variant and lacks the proline-proline (986-987 position) mutation present in other COVID-19 vaccines. This Phase 1 observer-blinded, randomized, placebo-controlled, ascending dose study evaluated the safety, tolerability, and immunogenicity of two doses of PTX-COVID19-B vaccine in healthy seronegative adults. Participants received two intramuscular doses, 4 weeks apart, of 16-μg, 40-μg, or 100-μg PTX-COVID19-B. Adverse events were generally mild to moderate, self-resolving, and transient. The most common solicited local and systemic adverse event was pain at the injection site and headache, respectively. After the first immunization, all participants seroconverted, producing high titers of anti-receptor-binding-domain, anti-Spike, and neutralizing antibodies, including neutralizing antibodies against the ancestral viral strain and the Alpha, Beta, and Delta variants of concern, in a dose-dependent way, further increasing over 10-20 times after the second dose. All tested doses of PTX-COVID19-B were safe, well-tolerated, and provided a strong immunogenicity response. The 40-μg dose showed fewer adverse reactions than the 100-μg dose, supporting further investigation of the 40-μg dose. Clinical Trial Registration [ClinicalTrials.gov][1] identifier: [NCT04765436][2] () ### Competing Interest Statement N.M.O., L.W., Y.A., B.S., E.G.M., and P.P. are employees of PT. PT received funding for the Phase 1 trial from National Research Council Canada. The development of the B.1.617.2 (Delta) lentiviral assay was supported by the CIHR operating grant to the Coronavirus Variants Rapid Response Network (CoVaRR-Net) to A.-C.G. A.-C.G. is the Canada Research Chair, Tier 1, in Functional Proteomics. ### Clinical Trial NCT04765436 ### Funding Statement Providence Therapeutics received funding for the Phase 1 trial from National Research Council Canada. ### 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 trial got full ethics approval from Advarra 372 Hollandview Trail, Suite 300 Aurora, ON L4G 0A5 Canada IORG Number: 0000635 IRB Registration: 00000971 FWA Number: 00023875 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.The development of the B.1.617.2 (Delta) lentiviral assay was supported by the CIHR operating grant to the Coronavirus Variants Rapid Response Network (CoVaRR-Net) to A.-C.G. A.-C.G. is the Canada Research Chair, Tier 1, in Functional Proteomics. [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04765436&atom=%2Fmedrxiv%2Fearly%2F2022%2F05%2F10%2F2022.05.06.22274690.atom