| Autor: |
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, Kiat Ruxrungtham |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-15 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-37795-0 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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