Immunogenicity and efficacy testing in chimpanzees of an oral hepatitis B vaccine based on live recombinant adenovirus.
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 hepatitis 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.
Lubeck
M D
MD
Wyeth-Ayerst Research, Biotechnology and Microbiology Division, Philadelphia, PA 19101.
Davis
A R
AR
Chengalvala
M
M
Natuk
R J
RJ
Morin
J E
JE
Molnar-Kimber
K
K
Mason
B B
BB
Bhat
B M
BM
Mizutani
S
S
Hung
P P
PP
D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D000284:Administration, Oral; D000818:Animals; D002460:Cell Line; D005796:Genes; D005801:Genes, Homeobox; D005814:Genes, Viral; D006509:Hepatitis B / Q000517:prevention & control*; D006514:Hepatitis B Surface Antigens / Q000235:genetics; D017325:Hepatitis B Vaccines; D006515:Hepatitis B virus / Q000235:genetics; D006801:Humans; D007117:Immunization, Secondary; D002679:Pan troglodytes; D011401:Promoter Regions, Genetic; D014761:Viral Hepatitis Vaccines / Q000008:administration & dosage / Q000276:immunology*
D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D014761:Viral Hepatitis Vaccines