Protective immunity of plant-produced African horse sickness virus serotype 5 chimaeric virus-like particles (VLPs) and viral protein 2 (VP2) vaccines in IFNAR-/- mice

O’Kennedy, Martha M.; Coetzee, Peter; Koekemoer, Otto; Plessis, Lissinda H. Du; Lourens, Carina W.; Kwezi, Lusisizwe; Preez, Ilse du; Mamputha, Sipho; Mokoena, Nobalanda B.; Rutkowska, Daria; Verschoor, J.A.; Lemmer, Yolandy

doi:10.1016/j.vaccine.2022.06.079

Cited by 5 publications

(17 citation statements)

References 35 publications

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“…Numerous alternative vaccine initiatives to combat AHS in endemic countries and beyond the borders of Africa have previously been described [ 8 ] but none are commercially available and the initiative to develop modern safe and efficacious subunit vaccines remain elusive. One of the more promising subunit vaccines being developed are plant-produced virus-like particles (VLPs) as these are robust protein scaffolds exhibiting well-defined geometry and uniformity that mimic the overall structure of the native virions.…”

Section: Introductionmentioning

confidence: 99%

“…Plant-produced, homogenous AHSV-5 VLP-based vaccines, administered in a prime-boost regime, resulted in high antibody titres being elicited in guinea pigs and horses [ 11 , 12 ], but relatively low titres in horses when they were vaccinated with the chimaeric AHSV-6 VLPs [ 13 ] most likely due to the poor assembly of VLPs of serotype 6 at the time. Subsequently, protective immunity was demonstrated with fully assembled chimaeric AHSV-5 VLPs in IFNAR -/- mice [ 8 ]. Due to the complexity of successfully assembling four capsid proteins into a triple layer, to form AHS VLPs of each serotype, assembling all nine AHS serotypes individually remained challenging.…”

Section: Introductionmentioning

confidence: 99%

“…VP2 is the major determinant inducing serotype specific neutralising antibodies (nAbs) [ 7 , 14 ] and correct display of essential epitopes in their native conformation is imperative. It is well established that full length soluble VP2 is sufficient to induce protective immunity in mice [ 8 , 15 ] and horses [ 5 ] whilst insoluble VP2 results in poor immunogenicity [ 4 ]. Humoral immunity plays a pivotal role in protection against AHSV [ 3 , 16 , 17 ] but other mechanisms such as antibody-dependent cellular cytotoxicity (ADCC) or other cell-mediated responses cannot be ignored as contributing factors [ 5 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…Once again Interferon α/β receptor knock-out (IFNAR -/- ) mice served as a cost-effective model to precede horse trials in vaccine candidate testing. It was previously demonstrated that a plant-produced monovalent AHSV-5 VP2 vaccine eliciting a titre of 1:320, conferred protective immunity in IFNAR -/- mice [ 8 ]. Here, two consecutive immunogenicity studies were conducted in IFNAR -/- mice, to validate the plant-produced multivalent immunogens directly with the commercially available LAV vaccine.…”

Section: Introductionmentioning

confidence: 99%

“…It was evident from the first mice trial, that each serotype required a booster vaccination and subsequently mice were vaccinated with the VP2 antigens of all nine serotypes (nonavalent) in a prime boost regime which then elicited high neutralising antibody titres ranging from 1:112 to 1:320. In addition, to avoid licence agreements for the use of glyco-engineered Nicotiana benthamiana [ 20 ] used in the previous study [ 8 ] and thereby simplifying commercialisation, here the vaccine products were produced in wild type N . benthamiana .…”

Section: Introductionmentioning

confidence: 99%

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

O’Kennedy,

Roth,

Ebersohn

et al. 2024

PLoS ONE

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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.

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Section: Introductionmentioning

confidence: 99%