Calvo-Pinilla Eva, de la Poza Francisco, Gubbins Simon, Mertens Peter Paul Clement, Ortego Javier, Castillo-Olivares Javier
The Pirbright Institute, Pirbright, Woking, Surrey, United Kingdom.
Centro de Investigación en Sanidad Animal, CISA-INIA, Valdeolmos, Madrid, Spain.
Antiviral Res. 2015 Apr;116:27-33. doi: 10.1016/j.antiviral.2015.01.009. Epub 2015 Jan 30.
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.
先前的研究表明,表达非洲马瘟病毒血清型4 VP2蛋白的重组痘苗病毒安卡拉株(MVA)(MVA-VP2)可在马体内诱导病毒中和抗体,并保护干扰素α受体基因敲除小鼠(IFNAR -/-)免受攻击。后续实验表明,在攻击前1小时将抗血清从MVA-VP2免疫供体被动转移至受体小鼠,可提供完全的临床保护并显著降低病毒血症。这些研究已扩展至确定MVA-VP2疫苗诱导的抗血清在攻击前48小时或攻击后48小时给药时的保护作用。此外,还进行了脾细胞的被动转移,以评估其是否能赋予免疫未成熟受体小鼠一定程度的免疫力。因此,从接种了MVA-VP2或野生型MVA(MVA-wt)的小鼠组中收集抗血清和脾细胞,用于受体小鼠的被动免疫。随后,后者用AHSV-4进行攻击(连同适当的接种或未接种疫苗的对照动物),并通过比较治疗组和对照组之间的临床症状、致死率和病毒血症来评估保护效果。所有接受抗血清的小鼠均表现出对疾病的高度保护(即使在攻击后48小时免疫的小鼠中存活率也达100%),与对照组相比,病毒血症在统计学上显著降低。与接受MVA-wt接种小鼠脾细胞的小鼠相比,接受MVA-VP2接种小鼠脾细胞的小鼠组存活率仅为40%,病毒血症略有降低。这些结果证实了MVA-VP2疫苗接种所赋予的保护性免疫主要具有体液免疫性质,并显示了给予MVA-VP2特异性抗血清作为非洲马瘟病毒紧急治疗方法的潜力。