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The immunogenicity of recombinant vaccines based on modified Vaccinia Ankara (MVA) viruses expressing African horse sickness virus VP2 antigens depends on the levels of expressed VP2 protein delivered to the host

Calvo-Pinilla, Eva; Gubbins, Simon; Mertens, Peter P.C.; Ortego, Javier; Castillo-Olivares, Javier

The immunogenicity of recombinant vaccines based on modified Vaccinia Ankara (MVA) viruses expressing African horse sickness virus VP2 antigens depends on the levels of expressed VP2 protein delivered to the host Thumbnail


Authors

Eva Calvo-Pinilla

Simon Gubbins

Javier Ortego

Javier Castillo-Olivares



Abstract

African horse sickness (AHS) is a lethal equine disease transmitted by Culicoides biting midges and caused by African horse sickness virus (AHSV). AHS is endemic to sub-Saharan Africa, but devastating outbreaks have been recorded periodically outside this region. The perceived risk of an AHS outbreak occurring in Europe has increased following the frequent epidemics caused in ruminants by bluetongue virus, closely related to AHSV.

Attenuated vaccines for AHS are considered unsuitable for use in non-endemic countries due bio-safety concerns. Further, attenuated and inactivated vaccines are not compatible with DIVA (differentiate infected from vaccinated animals) strategies. All these factors stimulated the development of novel AHS vaccines that are safer, more efficacious and DIVA compatible.

We showed previously that recombinant modified Vaccinia Ankara virus (MVA) vaccines encoding the outer capsid protein of AHSV (AHSV-VP2) induced virus neutralising antibodies (VNAb) and protection against AHSV in a mouse model and also in the horse. Passive immunisation studies demonstrated that immunity induced by MVA-VP2 was associated with pre-challenge VNAb titres in the vaccinates. Analyses of the inoculum of these MVA-VP2 experimental vaccines showed that they contained pre-formed AHSV-VP2.

We continued studying the influence of pre-formed AHSV-VP2, present in the inoculum of MVA-VP2 vaccines, in the immunogenicity of MVA-VP2 vaccines. Thus, we compared correlates of immunity in challenged mice that were previously vaccinated with: a) MVA-VP2 (live); b) MVA-VP2 (live and sucrose gradient purified); c) MVA-VP2 (UV light inactivated); d) MVA-VP2 (UV light inactivated and diluted); e) MVA-VP2 (heat inactivated); f) MVA-VP2 (UV inactivated) + MVA-VP2 (purified); g) MVA-VP2 (heat inactivated) + MVA-VP2 (purified); and h) wild type-MVA (no insert). The results of these experiments showed that protection was maximal using MVA-VP2 (live) vaccine and that the protection conferred by all other vaccines correlated strongly with the levels of pre-formed AHSV-VP2 in the vaccine inoculum.

Citation

Calvo-Pinilla, E., Gubbins, S., Mertens, P. P., Ortego, J., & Castillo-Olivares, J. (2018). The immunogenicity of recombinant vaccines based on modified Vaccinia Ankara (MVA) viruses expressing African horse sickness virus VP2 antigens depends on the levels of expressed VP2 protein delivered to the host. Antiviral Research, 154, https://doi.org/10.1016/j.antiviral.2018.04.015

Journal Article Type Article
Acceptance Date Apr 17, 2018
Online Publication Date Apr 18, 2018
Publication Date Jun 30, 2018
Deposit Date Apr 30, 2018
Publicly Available Date Apr 30, 2018
Journal Antiviral Research
Print ISSN 0166-3542
Electronic ISSN 1872-9096
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 154
DOI https://doi.org/10.1016/j.antiviral.2018.04.015
Keywords African horse sickness; Vaccinia; MVA; VP2
Public URL https://nottingham-repository.worktribe.com/output/943822
Publisher URL https://doi.org/10.1016/j.antiviral.2018.04.015
Contract Date Apr 30, 2018

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