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De novo syntheses of Marburg virus antigens from adenovirus vectors induce potent humoral and cellular immune responses

机译：从腺病毒载体重新合成马尔堡病毒抗原可诱导有效的体液和细胞免疫反应

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摘要

Marburg virus (MARV) is an African filovirus that causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, there are no MARV vaccines or therapies approved for human use. We hypothesized that developing a vaccine that induces a de novo synthesis of MARV antigens in vivo will lead to strong induction of both a humoral and cell-mediated immune response against MARV. Here, we develop and characterize three novel gene-based vaccine candidates which express the viral glycoprotein (GP) from either the Ci67, Ravn or Musoke strain of MARV. Immunization of mice with complex adenovirus (Ad)-based vaccine candidates (cAdVax vaccines), led to efficient production of both antibodies and cytotoxic T lymphocytes (CTL) specific to Musoke strain GP and Ci67 strain GP, respectively. Antibody responses were also shown to be cross-reactive across the MARV strains, but not cross-reactive to Ebola virus, a related filovirus. Additionally, three 1x10(8)pfu doses of vaccine vector were demonstrated to be safe in mice, as this did not lead to any detectable toxicity in liver or spleen. These promising results indicate that a cAdVax-based vaccine could be effective for induction of both humoral and cell-mediated immune responses to multiple strains of the Marburg virus.
机译：马尔堡病毒（MARV）是一种非洲丝状病毒，可导致人类致命的出血热，死亡率高达90％。当前，尚无批准用于人类的MARV疫苗或疗法。我们假设开发一种在体内诱导从头合成MARV抗原的疫苗将导致对MARV的体液免疫和细胞介导的免疫反应的强烈诱导。在这里，我们开发和表征三个新的基于基因的候选疫苗，这些候选疫苗可表达来自MARV的Ci67，Ravn或Musoke株的病毒糖蛋白（GP）。用基于复杂腺病毒（Ad）的候选疫苗（cAdVax疫苗）对小鼠进行免疫，可分别有效生产对Musoke株GP和Ci67株GP特异性的抗体和细胞毒性T淋巴细胞（CTL）。抗体反应在MARV病毒株之间也有交叉反应，但与埃博拉病毒（一种相关的丝状病毒）没有交叉反应。此外，已证明三剂1x10（8）pfu剂量的疫苗载体在小鼠中是安全的，因为这不会对肝脏或脾脏产生任何可检测到的毒性。这些有希望的结果表明，基于cAdVax的疫苗可以有效诱导针对多种马尔堡病毒菌株的体液免疫和细胞介导的免疫反应。

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