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.Mahidol University2023-05-152023-05-152023-12-01Nature Communications Vol.14 No.1 (2023)https://repository.li.mahidol.ac.th/handle/20.500.14594/81312Establishment 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.Biochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1038/s41467-023-37795-02-s2.0-851535531482041172337085495