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

• Published in: Vaccine 2006-04, Vol.24 (15), p.2975-2986
• Main Authors: Wang, Danher, Schmaljohn, Alan L., Raja, Nicholas U., Trubey, Charles M., Juompan, Laure Y., Luo, Min, Deitz, Stephen B., Yu, Hong, Woraratanadharm, Jan, Holman, David H., Moore, Kevin M., Swain, Benjamin M., Pratt, William D., Dong, John Y.
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenovirus; Animals; Antibodies, Viral - blood; Antigens, Viral - biosynthesis; Antigens, Viral - genetics; Antigens, Viral - immunology; Applied microbiology; Biological and medical sciences; cAdVax; Ci67; Cross Reactions; Cytotoxicity Tests, Immunologic; Ebola virus; Enzyme-Linked Immunosorbent Assay; Filovirus; Fundamental and applied biological sciences. Psychology; Genetic Vectors; Humans; Immune response; Immune system; Immunization; Liver - pathology; Lymphocytes; Marburg virus; Marburg Virus Disease - immunology; Marburg Virus Disease - prevention & control; Marburgvirus - genetics; Marburgvirus - immunology; Mice; Mice, Inbred C57BL; Microbiology; Miscellaneous; Models, Animal; Mortality; Musoke; Ravn; Spleen - pathology; T-Lymphocytes, Cytotoxic - immunology; Vaccine; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral Envelope Proteins - biosynthesis; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; Viral Vaccines - administration & dosage; Viral Vaccines - adverse effects; Viral Vaccines - genetics; Viral Vaccines - immunology; Virology
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2005.11.046

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 1 × 10 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.