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

Eakachai Prompetchara, Chutitorn Ketloy (), Mohamad-Gabriel Alameh, Kittipan Tharakhet, Papatsara Kaewpang, Nongnaphat Yostrerat, Patrawadee Pitakpolrat, Supranee Buranapraditkun, Suwimon Manopwisedjaroen, Arunee Thitithanyanont, Anan Jongkaewwattana, Taweewan Hunsawong, Rawiwan Im-Erbsin, Matthew Reed, Wassana Wijagkanalan, Kanitha Patarakul, Teerasit Techawiwattanaboon, Tanapat Palaga, Kieu Lam, James Heyes, Drew Weissman and Kiat Ruxrungtham
Additional contact information
Eakachai Prompetchara: Chulalongkorn University
Chutitorn Ketloy: Chulalongkorn University
Mohamad-Gabriel Alameh: University of Pennsylvania Perelman School of Medicine
Kittipan Tharakhet: Chulalongkorn University
Papatsara Kaewpang: Chulalongkorn University
Nongnaphat Yostrerat: Chulalongkorn University
Patrawadee Pitakpolrat: Chulalongkorn University
Supranee Buranapraditkun: Chulalongkorn University
Suwimon Manopwisedjaroen: Mahidol University
Arunee Thitithanyanont: Mahidol University
Anan Jongkaewwattana: National Science and Technology Development Agency (NSTDA)
Taweewan Hunsawong: Armed Forces Research Institute of Medical Sciences (AFRIMS)
Rawiwan Im-Erbsin: USAMD-AFRIMS
Matthew Reed: USAMD-AFRIMS
Wassana Wijagkanalan: BioNet-Asia, Co. Ltd
Kanitha Patarakul: Chulalongkorn University
Teerasit Techawiwattanaboon: Chulalongkorn University
Tanapat Palaga: Chulalongkorn University
Kieu Lam: Genevant Sciences Corporation
James Heyes: Genevant Sciences Corporation
Drew Weissman: University of Pennsylvania Perelman School of Medicine
Kiat Ruxrungtham: Chulalongkorn University

Nature Communications, 2023, vol. 14, issue 1, 1-15

Abstract: 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-37795-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37795-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-37795-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().