Immunogenicity of a candidate live attenuated vaccine for Rift Valley fever virus with a two-segmented genome

Ayers, V. B., Huang, Y.-J. S., Dunlop, J. I., Kohl, A. , Brennan, B. , Higgs, S. and Vanlandingham, D. L. (2023) Immunogenicity of a candidate live attenuated vaccine for Rift Valley fever virus with a two-segmented genome. Viral Immunology, 36(1), pp. 33-40. (doi: 10.1089/vim.2022.0104) (PMID:36399689) (PMCID:PMC9885543)

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Abstract

Rift Valley fever virus (RVFV) is an emerging arbovirus that affects both ruminants and humans. RVFV causes severe and recurrent outbreaks in Africa and the Arabian Peninsula with a significant risk for emergence into new locations. Although there are a variety of RVFV veterinary vaccines for use in endemic areas, there is currently no licensed vaccine for human use; therefore, there is a need to develop and assess new vaccines. Herein, we report a live-attenuated recombinant vaccine candidate for RVFV, based on the previously described genomic reconfiguration of the conditionally licensed MP12 vaccine. There are two general strategies used to develop live-attenuated RVFV vaccines, one being serial passage of wild-type RVFV strains to select attenuated mutants such as Smithburn, Clone 13, and MP12 vaccine strains. The second strategy has utilized reverse genetics to attenuate RVFV strains by introducing deletions or insertions within the viral genome. The novel candidate vaccine characterized in this report contains a two-segmented genome that lacks the medium viral segment (M) and two virulence genes (nonstructural small and nonstructural medium). The vaccine candidate, named r2segMP12, was evaluated for the production of neutralizing antibodies to RVFV in outbred CD-1 mice. The immune response induced by the r2segMP12 vaccine candidate was directly compared to the immune response induced by the rMP12 parental strain vaccine. Our study demonstrated that a single immunization with the r2segMP12 vaccine candidate at 105 plaque-forming units elicited a higher neutralizing antibody response than the rMP12 vaccine at the same vaccination titer without the need for a booster.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Brennan, Dr Benjamin and Kohl, Professor Alain
Creator Roles:
Kohl, A.Validation, Resources, Writing – review and editing
Brennan, B.Validation, Resources, Writing – review and editing
Authors: Ayers, V. B., Huang, Y.-J. S., Dunlop, J. I., Kohl, A., Brennan, B., Higgs, S., and Vanlandingham, D. L.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Journal Name:Viral Immunology
Publisher:Mary Ann Liebert
ISSN:0882-8245
ISSN (Online):1557-8976
Published Online:18 November 2022
Copyright Holders:Copyright © 2022 Victoria B. Ayers et al.
First Published:First published in Viral Immunology 36(1): 33-40
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
171267US-UK BBSRC-NIFA Collab: Control of emerging bunyavirusesAlain KohlBiotechnology and Biological Sciences Research Council (BBSRC)BB/M027112/1III-MRC-GU 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