Antiserum from mice vaccinated with modified vaccinia Ankara virus expressing African horse sickness virus (AHSV) VP2 provides protection when it is administered 48h before, or 48h after challenge

Antiviral Res. 2015 Apr:116:27-33. doi: 10.1016/j.antiviral.2015.01.009. Epub 2015 Jan 30.

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.

Keywords: AHSV; African horse sickness; Humoral immunity; MVA-VP2; Passive immunisation; Protection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Horse Sickness / immunology*
  • African Horse Sickness / prevention & control*
  • African Horse Sickness / therapy
  • African Horse Sickness / virology
  • African Horse Sickness Virus / genetics
  • African Horse Sickness Virus / immunology*
  • Animals
  • Antibodies, Neutralizing / administration & dosage
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / administration & dosage
  • Antibodies, Viral / immunology*
  • Capsid Proteins / immunology*
  • Enzyme-Linked Immunospot Assay
  • Horses
  • Immunization, Passive*
  • Interferon-gamma / biosynthesis
  • Mice
  • Mice, Knockout
  • Receptor, Interferon alpha-beta / genetics
  • Spleen / cytology
  • Viral Vaccines / immunology*
  • Viral Vaccines / therapeutic use
  • Viremia / prevention & control

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Capsid Proteins
  • VP2 protein, African horse sickness virus
  • Viral Vaccines
  • Receptor, Interferon alpha-beta
  • Interferon-gamma