Immunogenicity and Efficacy Testing in Chimpanzees of an Oral Hepatitis B Vaccine Based on Live Recombinant Adenovirus

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 86; no. 17; pp. 6763 - 6767
• Main Authors: Lubeck, Michael D., Davis, Alan R., Chengalvala, Murty, Natuk, Robert J., Morin, John E., Molnar-Kimber, Katherine, Mason, Bruce B., Bhat, Bheem M., Mizutani, Satoshi, Hung, Paul P., Purcell, Robert H.
• Format: Journal Article
• Language: English
• Published: Washington, DC National Academy of Sciences of the United States of America 01-09-1989; National Acad Sciences
• Subjects: Adenoviruses; Adenoviruses, Human - genetics; Adenoviruses, Human - immunology; Administration, Oral; Animals; Antibodies; Biological and medical sciences; Capsules; Cell Line; Fundamental and applied biological sciences. Psychology; Genes; Genes, Homeobox; Genes, Viral; Hepatitis antigens; Hepatitis B - prevention & control; Hepatitis B Surface Antigens - genetics; Hepatitis B Vaccines; Hepatitis B virus; Hepatitis B virus - genetics; Humans; Immunization; Immunization, Secondary; Infections; Inoculation; Microbiology; Pan troglodytes; Promoter Regions, Genetic; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Viral Hepatitis Vaccines - administration & dosage; Viral Hepatitis Vaccines - immunology; Virology; Viruses; Immunization; Adenoviridae; Immune response; Vaccination; Monkey; Oral administration; Vaccine; Infection; Virus; Viral hepatitis B; Vertebrata; Mammalia; Immunogenicity; Hepadnaviridae; Viral disease; Human adenovirus; Primates; Mastadenovirus; Hepatitis B virus; Humoral immunity
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.86.17.6763

As a major cause of acute and chronic liver disease as well as hepatocellular carcinoma, hepatitis B virus (HBV) continues to pose significant health problems world-wide. Recombinant hepatitis B vaccines based on adenovirus vectors have been developed to address global needs for effective control of hepatitits B infection. Although considerable progress has been made in the construction of recombinant adenoviruses that express large amounts of HBV gene products, preclinical immunogenicity and efficacy testing of candidate vaccines has remained difficult due to the lack of a suitable animal model. We demonstrate here that chimpanzees are susceptible to enteric infection by human adenoviruses type 7 (Ad7) and type 4 (Ad4) following oral administration of live virus. Moreover, after sequential oral immunization with Ad7-and Ad4-vectored vaccines containing the hepatitis B surface antigen (HBsAg) gene, significant antibody responses to HBsAg (anti-HBs) were induced in two chimpanzees. After challenge with heterologous HBV, one chimpanzee was protected from acute hepatitis and the other chimpanzee experienced modified HBV-induced disease. These data demonstrate the feasibility of using orally administered recombinant adenoviruses as a general approach to vaccination.