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Protective efficacy of multivalent replication-abortive vaccine strains in horses against African horse sickness virus challenge

机译:多价复制性排毒疫苗株在马中对非洲马瘟病毒攻击的保护作用

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摘要

African horse sickness virus (AHSV) is an orbivirus, a member of the Reoviridae family. Nine different serotypes have been described so far. AHSV is vectored by Culicoides spp. to equids, causing high mortality, particularly in horses, with considerable economic impacts. For development of a safe attenuated vaccine, we previously established an efficient reverse genetics (RG) system to generate Entry Competent Replication-Abortive (ECRA) virus strains, for all nine serotypes and demonstrated the vaccine potential of these strains in type I interferon receptor (IFNAR)-knockout mice. Here, we evaluated the protective efficacies of these ECRA viruses in AHSV natural hosts. One monoserotype (ECRA.A4) vaccine and one multivalent cocktail (ECRA.A1/4/6/8) vaccine were tested in ponies and subsequently challenged with a virulent AHSV4. In contrast to control animals, all vaccinated ponies were protected and did not develop severe clinical symptoms of AHS. Furthermore, the multivalent cocktail vaccinated ponies produced neutralizing antibodies against all serotypes present in the cocktail, and a foal born during the trial was healthy and had no viremia. These results validate the suitability of these ECRA strains as a new generation of vaccines for AHSV.
机译:非洲马瘟病毒(AHSV)是一种呼肠孤病毒,是呼肠孤病毒科的成员。到目前为止,已经描述了九种不同的血清型。 AHSV是由Culicoides spp载体提供的。造成严重的经济影响,尤其是在马匹中,造成很高的死亡率。为了开发安全的减毒疫苗,我们先前建立了一个有效的反向遗传(RG)系统,以针对所有9种血清型产生进入竞争性复制-堕胎(ECRA)病毒株,并证明了这些菌株在I型干扰素受体中的疫苗潜力( IFNAR)基因敲除小鼠。在这里,我们评估了这些ECRA病毒在AHSV自然宿主中的保护作用。在小马中测试了一种单血清型(ECRA.A4)疫苗和一种多价鸡尾酒(ECRA.A1 / 4/6/8)疫苗,随后用强毒的AHSV4攻击。与对照动物相反,所有接种的小马均受到保护,没有出现严重的AHS临床症状。此外,多价鸡尾酒疫苗接种的小马产生了针对鸡尾酒中所有血清型的中和抗体,并且在试验期间出生的小马驹是健康的,没有病毒血症。这些结果证实了这些ECRA菌株作为AHSV的新一代疫苗的适用性。

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