Abstract
Previous studies show that a recombinant modified vaccinia Ankara (MVA) virus expressing VP2 of AHSV serotype 4 (MVA-VP2) induced virus neutralising antibodies in horses and protected interferon alpha receptor gene knock-out mice (IFNAR −/−) against challenge. Follow up experiments indicated that passive transfer of antiserum, from MVA-VP2 immune donors to recipient mice 1h before challenge, conferred complete clinical protection and significantly reduced viraemia.These studies have been extended to determine the protective effect of MVA-VP2 vaccine-induced antiserum, when administered 48h before, or 48h after challenge. In addition, passive transfer of splenocytes was undertaken to assess if they confer any degree of immunity to immunologically naïve recipient mice. Thus, antisera and splenocytes were collected from groups of mice that had been vaccinated with MVA-VP2, or wild type MVA (MVA-wt), for passive immunisation of recipient mice. The latter were subsequently challenged with AHSV-4 (together with appropriate vaccinated or unvaccinated control animals) and protection was assessed by comparing clinical signs, lethality and viraemia between treated and control groups. All antiserum recipients showed high protection against disease (100% survival rates even in mice that were immunised 48h after challenge) and statistically significant reduction or viraemia in comparison with the control groups. The mouse group receiving splenocytes from MVA-VP2 vaccinates, showed only a 40% survival rate, with a small reduction in viraemia, compared to those mice that had received splenocytes from MVA-wt vaccinates. These results confirm the primarily humoral nature of protective immunity conferred by MVA-VP2 vaccination and show the potential of administering MVA-VP2 specific antiserum as an emergency treatment for AHSV.
Highlights
African horse sickness (AHS) is an arthropod-borne viral disease of solipeds transmitted by haematophagous insects of the genus Culicoides, the horse being the most severely affected species
It has recently been demonstrated that immunologically naïve mice can be protected against challenge with a virulent strain of African horse sickness virus (AHSV)-4, by administering serum from mice previously vaccinated with MVA expressing AHSV VP2 (MVA-VP2))
These studies have been extended to determine: (a) whether adoptive transfer of splenocytes from MVA-VP2 vaccinates could protect against AHSV-4 infection; and (b) whether protection by passive immunisation with antibodies from MVA-VP2 vaccinated mice could be observed when administered 48 h before, or 48 h after the challenge
Summary
African horse sickness (AHS) is an arthropod-borne viral disease of solipeds transmitted by haematophagous insects of the genus Culicoides, the horse being the most severely affected species. All of the different isolates, strains and serotypes of African horse sickness virus (AHSV) are classified within the species African horse sickness virus, genus Orbivirus, family Reoviridae. AHSV is closely related to bluetongue virus, which causes bluetongue disease. The spherical, non-enveloped capsid of AHSV is approximately 70 nm in diameter, is composed of three concentric protein layers (Roy et al, 1994). The outer-capsid layer is formed by two major structural proteins, VP2 and VP5 (encoded by genome-segments 2 and 6 respectively), and is primarily involved in cell attachment and cell entry. VP2 is the most variable antigen of AHSV and is responsible for serotype definition (Burrage et al, 1993)
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