Adenovirus vectored vaccines

Dev Biol Stand. 1994;82:71-7.

Abstract

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)

MeSH terms

  • AIDS Vaccines* / immunology
  • Adenoviruses, Human / genetics*
  • Animals
  • Antibodies, Viral / biosynthesis*
  • Dogs
  • Enzyme-Linked Immunosorbent Assay
  • Gene Products, env / immunology
  • Gene Products, gag / immunology
  • Genetic Vectors*
  • HIV / immunology
  • HIV Antibodies / biosynthesis
  • HN Protein*
  • Hepatitis B Antibodies / biosynthesis
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B Vaccines* / immunology
  • Hepatitis B virus / immunology
  • Immunization, Secondary
  • Pan troglodytes
  • Respiratory Syncytial Viruses / immunology*
  • Vaccines, Synthetic* / immunology
  • Viral Envelope Proteins
  • Viral Proteins / immunology

Substances

  • AIDS Vaccines
  • Antibodies, Viral
  • Gene Products, env
  • Gene Products, gag
  • HIV Antibodies
  • HN Protein
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens
  • Hepatitis B Vaccines
  • Vaccines, Synthetic
  • Viral Envelope Proteins
  • Viral Proteins
  • attachment protein G