Adenovirus vectored vaccines.
Human recombinant adenoviruses (Ad) have been employed to develop experimental vaccines against a number of infectious agents. Ad-vectored vaccines express recombinant proteins, including any post-translational modifications, into functioning replicas of the native proteins capable of eliciting neutralizing antibodies in both abortive and permissive animal models. Human Ad types 4, 5, and 7 were used to construct recombinant viruses that express the respiratory syncytial virus F or G glycoproteins, the hepatitis B surface antigen, and the HIV env or gag genes. The recombinant Ad-HIV viruses are of particular interest and have been examined for their immunogenicity in dogs and chimpanzees. Dogs were immunized intratracheally with Ad-env recombinants (10(9) pfu/dog). Excellent humoral anti-HIV responses, including neutralizing antibodies, were detected in the sera following booster immunization (12-18 weeks after primary immunization) with a second Ad-env recombinant made in a different Ad serotype (heterotypic booster). Chimpanzees were immunized in two ways, orally with lyophilized virus (10(9) to 10(10) pfu/virus) in enteric-coated capsules or intranasally (10(7) pfu/virus). Intranasal immunization was superior to oral immunization with respect to replication of recombinant viruses as well as induction of anti-Ad and anti-HIV antibodies. Administration by both routes resulted in stimulation of cellular immune responses, as measured by antigen proliferation assays. Anti-HIV antibodies were detected in chimpanzee secretions (salivary, nasal, rectal, vaginal) taken from animals following intranasal immunization with a heterotypic recombinant. Intranasal administration effectively primed chimpanzees to produce high-titred (320-640) serum neutralizing antibodies to HIV following boosting with a baculovirus-derived env (gp160) subunit vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)
Natuk
R J
RJ
Wyeth-Ayerst Research, Biotechnology & Microbiology Division, Philadelphia, PA.
Davis
A R
AR
Chanda
P K
PK
Lubeck
M D
MD
Chengalvala
M
M
Murthy
S C
SC
Wade
M S
MS
Dheer
S K
SK
Bhat
B M
BM
Murthy
K K
KK
D016915:AIDS Vaccines / Q000276:immunology; D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis*; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D005822:Genetic Vectors; D006678:HIV / Q000276:immunology; D015483:HIV Antibodies / Q000096:biosynthesis; D015707:HN Protein; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000276:immunology; D006515:Hepatitis B virus / Q000276:immunology; D007117:Immunization, Secondary; D002679:Pan troglodytes; D012136:Respiratory Syncytial Viruses / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000276:immunology; D014759:Viral Envelope Proteins; D014764:Viral Proteins / Q000276:immunology
D016915:AIDS Vaccines; D000914:Antibodies, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D015483:HIV Antibodies; D015707:HN Protein; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; D014764:Viral Proteins; C116204:attachment protein G