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Virus-like particles of louping ill virus elicit potent neutralizing antibodies targeting multimers of viral envelope protein

Tandavanitj, Rapeepat, Setthapramote, Chayanee, De Lorenzo, Giuditta, Sanchez-Velazquez, Ricardo, Clark, Jordan J., Rocchi, Mara, McInnes, Colin, Kohl, Alain and Patel, Arvind H. (2024) 'Virus-like particles of louping ill virus elicit potent neutralizing antibodies targeting multimers of viral envelope protein'. Vaccine. (In Press)

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Abstract

Louping ill virus (LIV) is a tick-borne flavivirus that predominantly causes disease in livestock, especially sheep in the British Isles. A preventive vaccine, previously approved for veterinary use but now discontinued, was based on an inactivated whole virion that likely provided protection by induction of neutralizing antibodies recognizing the viral envelope (E) protein. A major disadvantage of the inactivated vaccine was the need for high containment facilities for the propagation of infectious virus, as mandated by the hazard group 3 status of the virus. This study aimed to develop high-efficacy non-infectious protein-based vaccine candidates. Specifically, soluble envelope protein (sE), and virus-like particles (VLPs), comprised of the precursor of membrane and envelope proteins, were generated, characterized, and studied for their immunogenicity in mice. Results showed that the VLPs induced more potent virus neutralizing response compared to sE, even though the total anti-envelope IgG content induced by the two antigens was similar. Depletion of anti-monomeric E protein antibodies from mouse immune sera suggested that the neutralizing antibodies elicited by the VLPs targeted epitopes spanning the highly organized structure of multimer of the E protein, whereas the antibody response induced by sE focused on E monomers. Thus, our results indicate that VLPs represent a promising LIV vaccine candidate.

Item Type: Article
Subjects: QU Biochemistry > Proteins. Amino Acids. Peptides > QU 55 Proteins
QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 575 Antibodies
WC Communicable Diseases > Virus Diseases > General Virus Diseases > WC 500 Virus diseases (General or not elsewhere classified)
Faculty: Department: Biological Sciences > Department of Tropical Disease Biology
Biological Sciences > Vector Biology Department
Digital Object Identifer (DOI): https://doi.org/10.1016/j.vaccine.2024.03.008
Depositing User: Amy Carroll
Date Deposited: 11 Mar 2024 11:10
Last Modified: 11 Mar 2024 11:10
URI: https://archive.lstmed.ac.uk/id/eprint/24182

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