Induction of Antibody Responses to African Horse Sickness Virus (AHSV) in Ponies after Vaccination with Recombinant Modified Vaccinia Ankara (MVA)

Abstract

BackgroundAfrican horse sickness virus (AHSV) causes a non-contagious, infectious disease in equids, with mortality rates that can exceed 90% in susceptible horse populations. AHSV vaccines play a crucial role in the control of the disease; however, there are concerns over the use of polyvalent live attenuated vaccines particularly in areas where AHSV is not endemic. Therefore, it is important to consider alternative approaches for AHSV vaccine development. We have carried out a pilot study to investigate the ability of recombinant modified vaccinia Ankara (MVA) vaccines expressing VP2, VP7 or NS3 genes of AHSV to stimulate immune responses against AHSV antigens in the horse.Methodology/Principal FindingsVP2, VP7 and NS3 genes from AHSV-4/Madrid87 were cloned into the vaccinia transfer vector pSC11 and recombinant MVA viruses generated. Antigen expression or transcription of the AHSV genes from cells infected with the recombinant viruses was confirmed. Pairs of ponies were vaccinated with MVAVP2, MVAVP7 or MVANS3 and both MVA vector and AHSV antigen-specific antibody responses were analysed. Vaccination with MVAVP2 induced a strong AHSV neutralising antibody response (VN titre up to a value of 2). MVAVP7 also induced AHSV antigen–specific responses, detected by western blotting. NS3 specific antibody responses were not detected.ConclusionsThis pilot study demonstrates the immunogenicity of recombinant MVA vectored AHSV vaccines, in particular MVAVP2, and indicates that further work to investigate whether these vaccines would confer protection from lethal AHSV challenge in the horse is justifiable.

Synthesis of empty african horse sickness virus particles

“…Over the years, vaccines based on baculovirus-expressed AHSV capsid proteins (Mart´nez-Torrecuadrada et al, 1994;Roy et al, 1996;Scanlen et al, 2002), DNA vaccines (Romito et al, 1999) and vaccines based on the use of poxvirus expression vectors (Chiam et al, 2009;Guthrie et al, 2009) have been pursued with varying degrees of success. A particularly promising approach for the development of an inherently safe AHS vaccine may be the production of virus-like particles (VLPs).…”

Immunoinformatics Prediction of Peptide-Based Vaccine Against African Horse Sickness Virus

“…The equine disease caused by the African Horse Sickness Virus (AHSV) often causes a mortality rate exceeding 90% in susceptible horse populations [45][46][47]. Attempts for protection and prevention from African horse sickness diseases has started as early as 1930's; when a prophylactic vaccination was carried out in South Africa in 1933 using a bivalent live AHS vaccine.…”

“…Other live attenuated vaccines were developed through years and currently there are commercially available for most AHSV serotypes [45,46,[48][49][50][51]. These vaccines are cheap and effective in producing a protective immunity following single inoculation, yet they have limitations; the biggest of which is the reassortment of the vaccine virus with wild-type virus strains in the mammalian host and/or insect [47,48,52].…”

“…This vaccine is believed to not only prevent the disease, but also to reduce the propagation of the virus by vectors, but it is not yet available in the market [45]. (VP2) and (VP5) genes of (AHSV-4) expressed by the Venezuelan equine encephalitis virus have been considered for a candidate recombinant (AHS) vaccine, however, they failed to induce neutralizing antibody in horse [47,50]. Canarypox virus vectored (ALVAC®) vaccine expressing the (VP2) and (VP5) of (AHSV-4) was also studied against African horse sickness virus (AHSV) infection and it gave promising results [52].…”

Invited presentations

“…Baculovirus expressed AHSV capsid proteins VP2, VP5, VP7 and VP3, either individually or combined to form virus-like particles (VLP), have shown promising results (Roy, 1994). The use of recombinant pox-virus vectors expressing these AHSV proteins have also shown potential as vaccines for AHS (Chiam et al, 2009;Guthrie et al, 2009).…”