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

Tandavanitj, R., Setthapramote, C., De Lorenzo, G. , Sanchez-Velazquez, R., Clark, J. J., Rocchi, M., McInnes, C., Kohl, A. and Patel, A. H. (2024) Virus-like particles of louping ill virus elicit potent neutralizing antibodies targeting multimers of viral envelope protein. Vaccine, (doi: 10.1016/j.vaccine.2024.03.008) (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:Articles
Additional Information:This research was funded by the Government Pharmaceutical Organization, Thailand (R.T.), Faculty of Medicine Vajira Hospital, Navamindradhiraj University (C.S.) and by the UK Medical Research Council grants MC_UU12014/2 (A.H.P) and MC_UU_12014/8 and MC_UU_00034/4 (A.K.).
Keywords:Louping ill virus, virus-like particles, VLPs, protein-based vaccines, neutralizing, antibodies.
Status:In Press
Refereed:Yes
Glasgow Author(s) Enlighten ID:Sanchez Velazquez, Ricardo and De Lorenzo, Dr Giuditta and Rocchi, Dr Mara and Tandavanitj, Rapeepat and CLARK, Jordan and Setthapramote, Dr Chayanee and Patel, Professor Arvind and Kohl, Professor Alain
Creator Roles:
Tandavanitj, R.Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Writing – original draft
Setthapramote, C.Formal analysis, Investigation, Methodology, Resources, Supervision, Visualization, Writing – original draft
De Lorenzo, G.Formal analysis, Investigation, Methodology, Validation, Supervision
Sanchez Velazquez, R.Methodology, Validation
CLARK, J.Formal analysis, Investigation, Methodology, Resources
Rocchi, M.Resources
Kohl, A.Conceptualization, Funding acquisition, Resources, Writing – original draft
Patel, A.Conceptualization, Funding acquisition, Methodology, Project administration, Resources, Supervision, Writing – original draft
Authors: Tandavanitj, R., Setthapramote, C., De Lorenzo, G., Sanchez-Velazquez, R., Clark, J. J., Rocchi, M., McInnes, C., Kohl, A., and Patel, A. H.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Vaccine
Publisher:Elsevier
ISSN:0264-410X
ISSN (Online):1873-2518
Published Online:08 March 2024
Copyright Holders:Copyright © 2024 The Authors
First Published:First published in Vaccine 2024
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
172630Basis of the host range and tissue tropism for hepatitis C virusArvind PatelMedical Research Council (MRC)MC_UU_12014/2III - Centre for Virus Research
172630007Arthropod-borne infections and emerging virus infections in high risk areas (Programme 4)Alain KohlMedical Research Council (MRC)MC_UU_12014/8III - Centre for Virus Research