Recent occurrences of filoviruses and the arenavirus Lassa virus (LASV) in overlapping endemic areas of Africa highlight the need for a prophylactic vaccine that would confer protection against all of these viruses that cause lethal hemorrhagic fever (HF). We developed a quadrivalent formulation of VesiculoVax that contains recombinant vesicular stomatitis virus (rVSV) vectors expressing filovirus glycoproteins and that also contains a rVSV vector expressing the glycoprotein of a lineage IV strain of LASV. Cynomolgus macaques were vaccinated twice with the quadrivalent formulation, followed by challenge 28 days after the boost vaccination with each of the 3 corresponding filoviruses (Ebola, Sudan, Marburg) or a heterologous contemporary lineage II strain of LASV. Serum IgG and neutralizing antibody responses specific for all 4 glycoproteins were detected in all vaccinated animals. A modest and balanced cell-mediated immune response specific for the glycoproteins was also detected in most of the vaccinated macaques. Regardless of the level of total glycoprotein-specific immune response detected after vaccination, all immunized animals were protected from disease and death following lethal challenges. These findings indicate that vaccination with attenuated rVSV vectors each expressing a single HF virus glycoprotein may provide protection against those filoviruses and LASV most commonly responsible for outbreaks of severe HF in Africa.

中文翻译：

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四价 VesiculoVax 疫苗可保护非人类灵长类动物免受病毒引起的出血热和死亡。


最近在非洲重叠流行区出现的丝状病毒和沙粒病毒拉沙病毒 (LASV) 凸显了对预防性疫苗的需求，该疫苗可以针对所有这些导致致命出血热 (HF) 的病毒提供保护。我们开发了 VesiculoVax 的四价制剂，其中含有表达丝状病毒糖蛋白的重组水泡性口炎病毒 (rVSV) 载体，还含有表达 LASV 谱系 IV 株糖蛋白的 rVSV 载体。食蟹猴用四价制剂接种两次，然后在加强接种后 28 天用 3 种相应的丝状病毒（埃博拉病毒、苏丹病毒、马尔堡病毒）或 LASV 的异源当代谱系 II 株进行攻击。在所有接种疫苗的动物中均检测到针对所有 4 种糖蛋白的血清 IgG 和中和抗体反应。在大多数接种疫苗的猕猴中也检测到了针对糖蛋白的适度且平衡的细胞介导的特异性免疫反应。无论疫苗接种后检测到的总糖蛋白特异性免疫反应水平如何，所有免疫动物在致命挑战后都免受疾病和死亡。这些发现表明，用表达单一心力衰竭病毒糖蛋白的减毒 rVSV 载体进行疫苗接种，可以针对那些最常导致非洲严重心力衰竭爆发的丝状病毒和 LASV 提供保护。