Replication and immunogenicity of Ad7-, Ad4-, and Ad5-hepatitis B virus surface antigen recombinants, with or without a portion of E3 region, in chimpanzees.
Human adenovirus vectors containing intact or largely deleted E3 region were used to construct adenovirus-hepatitis B recombinant viruses (Ad-HepB) and shown to produce substantial amount of recombinant protein, hepatitis B surface antigen (HBsAg), in tissue culture. Previously we showed that these viruses were able to elicit good anti-HBs antibodies in a dog model. In the present study, the Ad-HepB viruses were evaluated for replication and immunogenicity in chimpanzees which sustain permissive infection by human adenoviruses. Recombinants containing entire E3 region showed better replication pattern than their E3 deleted counterparts as evidenced by longer duration and high titers of virus shedding. The effect of E3 region was also seen in the antibody titers against HBsAg in that the E3 containing viruses showed better response than the E3 deleted viruses. The importance of E3 region for the development of adenovirus vectored vaccines is further discussed.
Chengalvala
M V
MV
Wyeth-Ayerst Research, Philadelphia, PA 19101, USA.
Bhat
B M
BM
Bhat
R A
RA
Dheer
S K
SK
Lubeck
M D
MD
Purcell
R H
RH
Murthy
K K
KK
D017503:Adenovirus E3 Proteins / Q000235:genetics / Q000276:immunology*; D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D000818:Animals; D005822:Genetic Vectors / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D002679:Pan troglodytes; D011993:Recombinant Fusion Proteins / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology*
D017503:Adenovirus E3 Proteins; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D011993:Recombinant Fusion Proteins