A Phase1 Results of a Non-Stabilized Spike-Encoding mRNA Vaccine in Adults

Background Effective COVID-19 mRNA vaccines are mainly available in high-income countries. ChulaCov19, a prefusion non-stabilized Spike protein-encoding, nucleoside-modified mRNA, lipid nanoparticle encapsulated vaccine development, aims to enhance accessibility of mRNA vaccine and future pandemic preparedness for low- to middle-income countries. Methods Seventy-two eligible volunteers, 36 aged 18-55 (adults) followed by 36 aged 56-75 (elderly) enrolled in a dose escalation study of ChulaCov19 mRNA vaccine. Two doses of vaccine were given 21 days apart at 10, 25, or 50 µg/dose (12/group). Safety was the primary and immunogenicity the secondary outcome. Human convalescents’ (HCS) and Pfizer/BioNTech vaccinees’ sera provided comparison panels. Results All three doses of ChulaCov19 were well tolerated and elicited robust dose-dependent and age- dependent B- and T-cell responses. Transient mild/moderate injection site pain, fever, chills, fatigue, and headache were more common after the second dose. Four weeks after the second ChulaCov19: dose at 10, 25, and 50 µg dose, MicroVNT-50 Geometric mean titer (GMT) against wild-type was 848, 736 and 1,140 IU/mL, respectively, versus 267 IU/mL for HCS. All dose levels elicited 100% seroconversion, with GMT ratio 4-8-fold higher than for HCS (p<0.01), and high IFNγ spot-forming cells/million peripheral blood mononuclear cells. The 50 µg dose induced better cross-neutralization against Alpha, Beta, Gamma, and Delta variants than lower doses. Conclusions ChulaCov19 at 50 µg/dose is well tolerated and elicited higher neutralizing antibodies than HCS with strong T-cell responses. These antibodies cross neutralized four variants of concern and ChulaCov19 has therefore proceeded to phase 2 and 3 clinical trials. Trial registration number [ClinicalTrials.gov][1] Identifier [NCT04566276][2] ![Figure][3] ### Competing Interest Statement Kiat Ruxrungtham, Drew Weissman, Mohamad Alameh, Chutitorn Ketloy, Eakachai Prompetchara, and Supranee Buranapraditkun are co-inventors of the submitted ChulaCov19 mRNA vaccine's Patent ### Clinical Trial NCT04566276 ### Clinical Protocols ### Funding Statement This study was funded by National Vaccine Institute (NVI), grant no. 2563. 1/ 11 and 2564.1/4; Chulalongkorn University Second Century Fund (C2F); the Ratchadapisek Sompoch Endowment Fund (2021), Chulalongkorn University (764002-HE04); and Public Donation through Covid-19 vaccine development fund of the Faculty of Medicine, Chulalongkorn University and the Thai Red Cross Society, Thailand. The authors would like to thank all the study participants without whose support the study would not have been possible. ### 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 and the Investigational New Drug application were approved by the ethics committee of the Faculty of Medicine, Chulalongkorn University, Bangkok, and Thailand's Food and Drug Administration, respectively. 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]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04566276&atom=%2Fmedrxiv%2Fearly%2F2022%2F05%2F16%2F2022.05.12.22274989.atom [3]: pending:yes