O’Kennedy, Martha MRoth, RobynEbersohn, KDu Plessis, LHMamputha, SiphoRutkowska, Daria ADu Preez, IlseVerschoor, JALemmer, Yolandy2024-09-132024-09-132024-04O’Kennedy, Martha M, Roth, R., Ebersohn, K., Du Plessis, L., Mamputha, S., Rutkowska, D.A., Du Preez, I. & Verschoor, J. et al. 2024. Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/-mice. <i>Plos One, 19(4).</i> http://hdl.handle.net/10204/137561932-6203https://doi.org/10.1371/journal.pone.0301340http://hdl.handle.net/10204/13756A 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 a/ß 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.FulltextenImmunogenic multivalent vaccineAfrican Horse Sickness virusAHSVPlant-produced AHS virus-like particlesSoluble viral protein 2VP2ArticleO’Kennedy, Martha M, Roth, R., Ebersohn, K., Du Plessis, L., Mamputha, S., Rutkowska, D. A., ... Lemmer, Y. (2024). Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/-mice. <i>Plos One, 19(4)</i>, http://hdl.handle.net/10204/13756O’Kennedy, Martha M, Robyn Roth, K Ebersohn, LH Du Plessis, Sipho Mamputha, Daria A Rutkowska, Ilse Du Preez, JA Verschoor, and Yolandy Lemmer "Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/-mice." <i>Plos One, 19(4)</i> (2024) http://hdl.handle.net/10204/13756O’Kennedy, Martha M, Roth R, Ebersohn K, Du Plessis L, Mamputha S, Rutkowska DA, et al. Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/-mice. Plos One, 19(4). 2024; http://hdl.handle.net/10204/13756.TY - Article AU - O’Kennedy, Martha M AU - Roth, Robyn AU - Ebersohn, K AU - Du Plessis, LH AU - Mamputha, Sipho AU - Rutkowska, Daria A AU - Du Preez, Ilse AU - Verschoor, JA AU - Lemmer, Yolandy AB - 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 a/ß 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. DA - 2024-04 DB - ResearchSpace DP - CSIR J1 - Plos One, 19(4) KW - Immunogenic multivalent vaccine KW - African Horse Sickness virus KW - AHSV KW - Plant-produced AHS virus-like particles KW - Soluble viral protein 2 KW - VP2 LK - https://researchspace.csir.co.za PY - 2024 SM - 1932-6203 T1 - Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/-mice TI - Immunogenic profile of a plant-produced nonavalent African horse sickness viral protein 2 (VP2) vaccine in IFNAR-/-mice UR - http://hdl.handle.net/10204/13756 ER -28073