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De Novo Synthesis of Marburg Virus Antigens from Adenovirus Vectors Induce Potent Humoral and Cellular Immune Responses

机译:De Novo从腺病毒载体合成马​​尔堡病毒抗原诱导有效的体液和细胞免疫应答

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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.

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