• Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice

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Metadata

Document Title

Immunogenicity and protective efficacy of SARS-CoV-2 mRNA vaccine encoding secreted non-stabilized spike in female mice

Author

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.

Affiliations

Center of Excellence in Vaccine Research and Development (Chula VRC), Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; Department of Laboratory Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; Integrated Frontier Biotechnology for Emerging Disease, Chulalongkorn University, Bangkok, 10330, Thailand; Division of Infectious Diseases, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, United States; Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; Thai Pediatric Gastroenterology, Hepatology and Immunology (TPGHAI) Research Unit, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, 10400, Thailand; Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani, 12120, Thailand; Department of Virology, Armed Forces Research Institute of Medical Sciences (AFRIMS), Bangkok, 10400, Thailand; Department of Veterinary Medicine, USAMD-AFRIMS, Bangkok, 10400, Thailand; BioNet-Asia, Co. Ltd, Bangkok, 10260, Thailand; Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand; Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, 10330, Thailand; Genevant Sciences Corporation, Vancouver, BC V5T 4T5, Canada; Department of Medicine, and School of Global Health, Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

Type

Article

Source Title

Nature Communications

ISSN

20411723

Year

2023

Volume

14

Issue

1

Page

-

Open Access

All Open Access, Gold

Publisher

Nature Research

DOI

10.1038/s41467-023-37795-0

Format

PDF

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. © 2023, The Author(s).

Funding Sponsor

Chulalongkorn University; National Research Council of Thailand; Faculty of Medicine, Chulalongkorn University

Publication Source

WOS

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