Chimeric Virus-like Particle-Based COVID-19 Vaccine Confers Strong Protection against SARS-CoV-2 Viremia in K18-hACE2 Mice.

Autor: Kaewborisuth C; Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand., Wanitchang A; Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand., Koonpaew S; Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand., Srisutthisamphan K; Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand., Saenboonrueng J; Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand., Im-Erbsin R; Department of Veterinary Medicine, U.S. Army Medical Directorate-Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand., Inthawong M; Department of Veterinary Medicine, U.S. Army Medical Directorate-Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand., Sunyakumthorn P; Department of Veterinary Medicine, U.S. Army Medical Directorate-Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand., Thaweerattanasinp T; Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand., Tanwattana N; Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand.; Interdisciplinary Program in Genetic Engineering and Bioinformatics, Graduate School, Kasetsart University, Bangkok 10900, Thailand., Jantraphakorn Y; Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand., Reed MC; Department of Veterinary Medicine, U.S. Army Medical Directorate-Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand., Lugo-Roman LA; Department of Veterinary Medicine, U.S. Army Medical Directorate-Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand., Hunsawong T; Department of Virology, U.S. Army Medical Directorate-Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand., Klungthong C; Department of Virology, U.S. Army Medical Directorate-Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand., Jones AR; Department of Virology, U.S. Army Medical Directorate-Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand., Fernandez S; Department of Virology, U.S. Army Medical Directorate-Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand., Teeravechyan S; Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand., Lombardini ED; U.S. Army Medical Directorate-Armed Forces Research Institute of Medical Sciences, Bangkok 10400, Thailand., Jongkaewwattana A; Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand.
Jazyk: angličtina
Zdroj: Vaccines [Vaccines (Basel)] 2022 May 16; Vol. 10 (5). Date of Electronic Publication: 2022 May 16.
DOI: 10.3390/vaccines10050786
Abstrakt: Virus-like particles (VLPs) are highly immunogenic and versatile subunit vaccines composed of multimeric viral proteins that mimic the whole virus but lack genetic material. Due to the lack of infectivity, VLPs are being developed as safe and effective vaccines against various infectious diseases. In this study, we generated a chimeric VLP-based COVID-19 vaccine stably produced by HEK293T cells. The chimeric VLPs contain the influenza virus A matrix (M1) proteins and the SARS-CoV-2 Wuhan strain spike (S) proteins with a deletion of the polybasic furin cleavage motif and a replacement of the transmembrane and cytoplasmic tail with that of the influenza virus hemagglutinin (HA). These resulting chimeric S-M1 VLPs, displaying S and M1, were observed to be enveloped particles that are heterogeneous in shape and size. The intramuscular vaccination of BALB/c mice in a prime-boost regimen elicited high titers of S-specific IgG and neutralizing antibodies. After immunization and a challenge with SARS-CoV-2 in K18-hACE2 mice, the S-M1 VLP vaccination resulted in a drastic reduction in viremia, as well as a decreased viral load in the lungs and improved survival rates compared to the control mice. Balanced Th1 and Th2 responses of activated S-specific T-cells were observed. Moderate degrees of inflammation and viral RNA in the lungs and brains were observed in the vaccinated group; however, brain lesion scores were less than in the PBS control. Overall, we demonstrate the immunogenicity of a chimeric VLP-based COVID-19 vaccine which confers strong protection against SARS-CoV-2 viremia in mice.
Databáze: MEDLINE
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