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.
Highlights
African horse sickness (AHS) is an arthropod-borne viral disease of solipeds transmitted by haematophagus insects of the genus Culicoides, the horse being the most severely affected species
In order to investigate the immunogenicity of modified Vaccinia Ankara virus (MVA)-VP2 vaccines in relation to pre-formed African horse sickness virus (AHSV)-VP2 present in the inoculum, we conducted two vaccination experiments using various MVA-VP2 vaccine preparations
The immunogenicity of these vaccines would rely only on the presence of pre-formed AHSV-VP2 in the inoculum and not on VP2 protein synthesised de novo from MVA-VP2 infected host cells
Summary
African horse sickness (AHS) is an arthropod-borne viral disease of solipeds transmitted by haematophagus insects of the genus Culicoides, the horse being the most severely affected species. The disease is caused by African horse sickness virus (AHSV), a member of the genus Orbivirus, family Reoviridae, closely related to bluetongue virus (BTV). The non-enveloped 55–70 nm AHSV spherical virion consists of a triplelayered capsid surrounding ten double-stranded RNA segments and three proteins involved in viral replication (VP1, VP4 and VP6, encoded by segments 1, 4 and 9 respectively) (Roy et al, 1994; Manole et al, 2012). The outer capsid is formed by two major structural proteins, VP2 and VP5 (encoded by segments 2 and 6 respectively), involved in cell attachment and entry. VP2 is the most variable antigen of AHSV, determines serotype formation (Burrage et al, 1993) and contains most of the virus neutralising antibody (VNAb) epitopes identified so far (Bentley et al, 2000; Burrage et al, 1993; Martinez-Torrecuadrada et al, 1999)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
