Important note: Information in this article was accurate in 1993. The state of the art may have changed since the publication date.
Immunogenicity of recombinant human adenovirus-human immunodeficiency virus vaccines in chimpanzees.
AIDS Res Hum Retroviruses. 1993 May;9(5):395-404. Unique Identifier : AIDSLINE MED/93305378 Natuk RJ; Lubeck MD; Chanda PK; Chengalvala M; Wade MS; Murthy SC; Wilhelm J; Vernon SK; Dheer SK; Mizutani S; et al; Wyeth-Ayerst Research, Biotechnology and Microbiology Division,; Philadelphia, PA 19101.
Abstract:
Recombinant human adenovirus (Ad) type 4-, 5-, and 7-vectored vaccines expressing either the HIV env or gag-protease genes were tested for immunogenicity in three chimpanzees. The first phase of the vaccination protocol consisted of a primary and two booster immunizations with Ad-HIVs by the oral route of administration, followed by a single booster immunization with Gag and/or Env subunit vaccines. The second phase of the vaccination protocol consisted of intranasal administration of Ad-HIVs previously administered by the oral route. Following the first phase adenovirus was shed into stools for only 1-7 days and modest type-specific anti-adenovirus neutralizing antibody titers were induced. Strong anti-Env binding antibody responses were detected in all three animals following the second oral booster immunization. One chimpanzee responded with a low-titered type-specific neutralizing antibody response to HIV. Cell-mediated immune responses to Env were not detected after the primary vaccination, but were detected following all booster immunizations. Administration of the Gag subunit vaccine boosted both humoral and cell-mediated immune responses to Gag antigens. In contrast, the Env subunit vaccine boosted cellular but not humoral immune responses. In the second phase of the vaccination protocol, both virus shedding and anti-adenovirus responses were enhanced. All three chimpanzees responded to the intranasal administration of Ad7-HIVs with boosted anti-HIV serum responses, including low-titered type-specific neutralizing antibodies, elicited anti-HIV antibodies at secretory sites, and stimulated cell-mediated immune responses to both Gag and Env antigens.
Keywords: Adenoviruses, Human/GENETICS/IMMUNOLOGY/PHYSIOLOGY Administration, Oral Animal Antibodies, Viral/BIOSYNTHESIS AIDS Vaccines/ADMINISTRATION & DOSAGE/*PHARMACOLOGY Base Sequence Chimpansee troglodytes DNA, Viral/GENETICS Gene Products, env/IMMUNOLOGY Gene Products, gag/IMMUNOLOGY Human HIV Antibodies/BIOSYNTHESIS HIV Antigens HIV-1/GENETICS/*IMMUNOLOGY/PHYSIOLOGY Immunity, Cellular Immunization, Secondary Molecular Sequence Data Vaccines, Synthetic/ADMINISTRATION & DOSAGE/PHARMACOLOGY Viral Vaccines/ADMINISTRATION & DOSAGE/PHARMACOLOGY Virus Replication JOURNAL ARTICLE 931030
M93A0727
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