Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/- mice.

Autor: O'Kennedy MM; Council for Scientific and Industrial Research (CSIR), Chemical Cluster, Pretoria, South Africa., Roth R; Council for Scientific and Industrial Research (CSIR), Chemical Cluster, Pretoria, South Africa., Ebersohn K; Department of Veterinary Tropical Diseases, University of Pretoria, Pretoria, South Africa., du Plessis LH; Centre of Excellence for Pharmaceutical Sciences (PharmacenTM), North-West University, Potchefstroom, South Africa., Mamputha S; Council for Scientific and Industrial Research (CSIR), Chemical Cluster, Pretoria, South Africa., Rutkowska DA; Council for Scientific and Industrial Research (CSIR), Chemical Cluster, Pretoria, South Africa., du Preez I; Council for Scientific and Industrial Research (CSIR), Chemical Cluster, Pretoria, South Africa., Verschoor JA; Department of Biochemistry, University of Pretoria, Pretoria, South Africa., Lemmer Y; Council for Scientific and Industrial Research (CSIR), Chemical Cluster, Pretoria, South Africa.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Apr 16; Vol. 19 (4), pp. e0301340. Date of Electronic Publication: 2024 Apr 16 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0301340
Abstrakt: A safe, highly immunogenic multivalent vaccine to protect against all nine serotypes of African horse sickness virus (AHSV), will revolutionise the AHS vaccine industry in endemic countries and beyond. Plant-produced AHS virus-like particles (VLPs) and soluble viral protein 2 (VP2) vaccine candidates were developed that have the potential to protect against all nine serotypes but can equally well be formulated as mono- and bi-valent formulations for localised outbreaks of specific serotypes. In the first interferon α/β receptor knock-out (IFNAR-/-) mice trial conducted, a nine-serotype (nonavalent) vaccine administered as two pentavalent (5 μg per serotype) vaccines (VLP/VP2 combination or exclusively VP2), were directly compared to the commercially available AHS live attenuated vaccine. In a follow up trial, mice were vaccinated with an adjuvanted nine-serotype multivalent VP2 vaccine in a prime boost strategy and resulted in the desired neutralising antibody titres of 1:320, previously demonstrated to confer protective immunity in IFNAR-/- mice. In addition, the plant-produced VP2 vaccine performed favourably when compared to the commercial vaccine. Here we provide compelling data for a nonavalent VP2-based vaccine candidate, with the VP2 from each serotype being antigenically distinguishable based on LC-MS/MS and ELISA data. This is the first preclinical trial demonstrating the ability of an adjuvanted nonavalent cocktail of soluble, plant-expressed AHS VP2 proteins administered in a prime-boost strategy eliciting high antibody titres against all 9 AHSV serotypes. Furthermore, elevated T helper cells 2 (Th2) and Th1, indicative of humoral and cell-mediated memory T cell immune responses, respectively, were detected in mouse serum collected 14 days after the multivalent prime-boost vaccination. Both Th2 and Th1 may play a role to confer protective immunity. These preclinical immunogenicity studies paved the way to test the safety and protective efficacy of the plant-produced nonavalent VP2 vaccine candidate in the target animals, horses.
Competing Interests: The authors have read the journal’s policy and have the following competing interests: Plant-produced chimaeric Orbivirus VLPs is patent protected (PCT/IB2017/052236, WO 2017/182958 A1, US 11,053,509 B2, ARIPO AP 6697 registered, invented by authors DR and MMO). The AHSV VP2 fusions proteins are protected by a patent application (PCT/IB2023/058808, invented by MMO and YL). This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no additional patents, products in development or marketed products associated with this research to declare
(Copyright: © 2024 O’Kennedy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje