Safety and immunogenicity of a prefusion non-stabilized spike protein mRNA COVID-19 vaccine: a phase I trial
Issued Date
2022-12-01
Resource Type
eISSN
20585276
Scopus ID
2-s2.0-85142076956
Pubmed ID
36376393
Journal Title
Nature Microbiology
Volume
7
Issue
12
Start Page
1987
End Page
1995
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Microbiology Vol.7 No.12 (2022) , 1987-1995
Suggested Citation
Gatechompol S., Kittanamongkolchai W., Ketloy C., Prompetchara E., Thitithanyanont A., Jongkaewwattana A., Buranapraditkun S., Alameh M.G., Ubolyam S., Sophonphan J., Apornpong T., Kerr S., Kamarulzaman A., Siwamogsatham S., Kroon E., Puthanakit T., Patarakul K., Palaga T., Wijagkanalan W., Carpenter A., Hong L., Weissman D., Ruxrungtham K. Safety and immunogenicity of a prefusion non-stabilized spike protein mRNA COVID-19 vaccine: a phase I trial. Nature Microbiology Vol.7 No.12 (2022) , 1987-1995. 1995. doi:10.1038/s41564-022-01271-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/83513
Title
Safety and immunogenicity of a prefusion non-stabilized spike protein mRNA COVID-19 vaccine: a phase I trial
Author(s)
Gatechompol S.
Kittanamongkolchai W.
Ketloy C.
Prompetchara E.
Thitithanyanont A.
Jongkaewwattana A.
Buranapraditkun S.
Alameh M.G.
Ubolyam S.
Sophonphan J.
Apornpong T.
Kerr S.
Kamarulzaman A.
Siwamogsatham S.
Kroon E.
Puthanakit T.
Patarakul K.
Palaga T.
Wijagkanalan W.
Carpenter A.
Hong L.
Weissman D.
Ruxrungtham K.
Kittanamongkolchai W.
Ketloy C.
Prompetchara E.
Thitithanyanont A.
Jongkaewwattana A.
Buranapraditkun S.
Alameh M.G.
Ubolyam S.
Sophonphan J.
Apornpong T.
Kerr S.
Kamarulzaman A.
Siwamogsatham S.
Kroon E.
Puthanakit T.
Patarakul K.
Palaga T.
Wijagkanalan W.
Carpenter A.
Hong L.
Weissman D.
Ruxrungtham K.
Author's Affiliation
Thai Red Cross Agency
Universiti Malaya
Chulalongkorn University
The Kirby Institute
The HIV Netherlands Australia Thailand Research Collaboration
Mahidol University
Thailand National Center for Genetic Engineering and Biotechnology
University of Pennsylvania Perelman School of Medicine
Faculty of Medicine, Chulalongkorn University
Genevant Sciences Corporation
Institute of HIV Research and Innovation
Co. Ltd.
Universiti Malaya
Chulalongkorn University
The Kirby Institute
The HIV Netherlands Australia Thailand Research Collaboration
Mahidol University
Thailand National Center for Genetic Engineering and Biotechnology
University of Pennsylvania Perelman School of Medicine
Faculty of Medicine, Chulalongkorn University
Genevant Sciences Corporation
Institute of HIV Research and Innovation
Co. Ltd.
Other Contributor(s)
Abstract
Effective mRNA SARS-CoV-2 vaccines are available but need to be stored in freezers, limiting their use to countries that have appropriate storage capacity. ChulaCov19 is a prefusion non-stabilized SARS-CoV-2 spike-protein-encoding, nucleoside-modified mRNA, lipid nanoparticle encapsulated vaccine that we report to be stable when stored at 2–8 °C for up to 3 months. Here we report safety and immunogenicity data from a phase I open-label, dose escalation, first-in-human trial of the ChulaCov19 vaccine (NCT04566276). Seventy-two eligible volunteers, 36 of whom were aged 18–55 (adults) and 36 aged 56–75 (elderly), were enroled. Two doses of vaccine were administered 21 d apart at 10, 25 or 50 μg per dose (12 per group). The primary outcome was safety and the secondary outcome was immunogenicity. All three dosages 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 dose, in the adult cohort, MicroVNT-50 geometric mean titre against wild-type SARS-CoV-2 was 848 (95% CI, 483–1,489), 736 (459–1,183) and 1,140 (854–1,522) IU ml−1 at 10, 25 and 50 μg doses, respectively, versus 285 (196–413) IU ml−1 for human convalescent sera. All dose levels elicited 100% seroconversion, with geometric mean titre ratios 4–8-fold higher than for human convalescent sera (P < 0.01), and high IFNγ spot-forming cells per million peripheral blood mononuclear cells. The 50 μg dose induced better cross-neutralization against Alpha, Beta, Gamma and Delta variants than lower doses. ChulaCov19 at 50 μg is well tolerated and elicited higher neutralizing antibodies than human convalescent sera, with strong T-cell responses. These antibodies cross-neutralized four variants of concern. ChulaCov19 has proceeded to phase 2 clinical trials. We conclude that the mRNA vaccine expressing a prefusion non-stabilized spike protein is safe and highly immunogenic.