Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice
1
Issued Date
2023-12-01
Resource Type
eISSN
20411723
Scopus ID
2-s2.0-85153553148
Pubmed ID
37085495
Journal Title
Nature Communications
Volume
14
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Nature Communications Vol.14 No.1 (2023)
Suggested Citation
Prompetchara E., Ketloy C., Alameh M.G., Tharakhet K., Kaewpang P., Yostrerat N., Pitakpolrat P., Buranapraditkun S., Manopwisedjaroen S., Thitithanyanont A., Jongkaewwattana A., Hunsawong T., Im-Erbsin R., Reed M., Wijagkanalan W., Patarakul K., Techawiwattanaboon T., Palaga T., Lam K., Heyes J., Weissman D., Ruxrungtham K. Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice. Nature Communications Vol.14 No.1 (2023). doi:10.1038/s41467-023-37795-0 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/81312
Title
Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice
Author(s)
Prompetchara E.
Ketloy C.
Alameh M.G.
Tharakhet K.
Kaewpang P.
Yostrerat N.
Pitakpolrat P.
Buranapraditkun S.
Manopwisedjaroen S.
Thitithanyanont A.
Jongkaewwattana A.
Hunsawong T.
Im-Erbsin R.
Reed M.
Wijagkanalan W.
Patarakul K.
Techawiwattanaboon T.
Palaga T.
Lam K.
Heyes J.
Weissman D.
Ruxrungtham K.
Ketloy C.
Alameh M.G.
Tharakhet K.
Kaewpang P.
Yostrerat N.
Pitakpolrat P.
Buranapraditkun S.
Manopwisedjaroen S.
Thitithanyanont A.
Jongkaewwattana A.
Hunsawong T.
Im-Erbsin R.
Reed M.
Wijagkanalan W.
Patarakul K.
Techawiwattanaboon T.
Palaga T.
Lam K.
Heyes J.
Weissman D.
Ruxrungtham K.
Author's Affiliation
Chulalongkorn University
Armed Forces Research Institute of Medical Sciences, Thailand
Mahidol University
Thailand National Center for Genetic Engineering and Biotechnology
University of Pennsylvania Perelman School of Medicine
Faculty of Medicine, Chulalongkorn University
USAMD-AFRIMS
Genevant Sciences Corporation
Ltd.
Armed Forces Research Institute of Medical Sciences, Thailand
Mahidol University
Thailand National Center for Genetic Engineering and Biotechnology
University of Pennsylvania Perelman School of Medicine
Faculty of Medicine, Chulalongkorn University
USAMD-AFRIMS
Genevant Sciences Corporation
Ltd.
Other Contributor(s)
Abstract
Establishment of an mRNA vaccine platform in low- and middle-income countries (LMICs) is important to enhance vaccine accessibility and ensure future pandemic preparedness. Here, we describe the preclinical studies of “ChulaCov19”, a SARS-CoV-2 mRNA encoding prefusion-unstabilized ectodomain spike protein encapsulated in lipid nanoparticles (LNP). In female BALB/c mice, ChulaCov19 at 0.2, 1, 10, and 30 μg elicits robust neutralizing antibody (NAb) and T cell responses in a dose-dependent relationship. The geometric mean titers (GMTs) of NAb against wild-type (WT, Wuhan-Hu1) virus are 1,280, 11,762, 54,047, and 62,084, respectively. Higher doses induce better cross-NAb against Delta (B.1.617.2) and Omicron (BA.1 and BA.4/5) variants. This elicited immunogenicity is significantly higher than those induced by homologous CoronaVac or AZD1222 vaccination. In a heterologous prime-boost study, ChulaCov19 booster dose generates a 7-fold increase of NAb against Wuhan-Hu1 WT virus and also significantly increases NAb response against Omicron (BA.1 and BA.4/5) when compared to homologous CoronaVac or AZD1222 vaccination. Challenge studies show that ChulaCov19 protects human-ACE-2-expressing female mice from COVID-19 symptoms, prevents viremia and significantly reduces tissue viral load. Moreover, anamnestic NAb response is undetectable in challenge animals. ChulaCov19 is therefore a promising mRNA vaccine candidate either as a primary or boost vaccination and has entered clinical development.