Protective immunization of horses with a recombinant canarypox virus vectored vaccine co-expressing genes encoding the outer capsid proteins of African horse sickness virus

Abstract

We describe the development and preliminary characterization of a recombinant canarypox virus vectored (ALVAC ® ) vaccine for protective immunization of equids against African horse sickness virus (AHSV) infection. Horses (n = 8) immunized with either of two concentrations of recombinant canarypox virus vector (ALVAC-AHSV) co-expressing synthetic genes encoding the outer capsid proteins (VP2 and VP5) of AHSV serotype 4 (AHSV-4) developed variable titres (<10-80) of virus-specific neutralizing antibodies and were completely resistant to challenge infection with a virulent strain of AHSV-4. In contrast, a horse immunized with a commercial recombinant canarypox virus vectored vaccine expressing the haemagglutinin genes of two equine influenza H3N8 viruses was seronegative to AHSV and following infection with virulent AHSV-4 developed pyrexia, thrombocytopenia and marked oedema of the supraorbital fossae typical of the "dikkop" or cardiac form of African horse sickness. AHSV was detected by virus isolation and quantitative reverse transcriptase polymerase chain reaction in the blood of the control horse from 8 days onwards after challenge infection whereas AHSV was not detected at any time in the blood of the ALVAC-AHSV vaccinated horses. The control horse seroconverted to AHSV by 2 weeks after challenge infection as determined by both virus neutralization and ELISA assays, whereas six of eight of the ALVAC-AHSV vaccinated horses did not seroconvert by either assay following challenge infection with virulent AHSV-4. These data confirm that the ALVAC-AHSV vaccine will be useful for the protective immunization of equids against African horse sickness, and avoids many of the problems inherent to liveattenuated AHSV vaccines.

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

“…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].…”

“…Pep fold available at the mobyle web server was used to predict the peptides structure. The five peptides that bound the largest number of alleles were selected for PepFold server [41,42] which produced five models (3D peptide structure) for each peptide. The proposed models for each of the selected MHC class I binding peptides were docked with the refrence MHC class I protein using Patch dock server with a Clustering Root Mean Square Deviation value of 1.5 (clustering RMSD=1.5) and a complex type of Protein -small ligand [43,44].…”

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).…”