IMMUNOGENICITY OF RECOMBINANT HUMAN ADENOVIRUS HUMAN-IMMUNODEFICIENCY-VIRUS VACCINES IN CHIMPANZEES

Recombinant human adenovirus (Ad) type 4-, 5-, and 7-vectored vaccines expressing either the HIV env or gag-protease genes were tested for i mmunogenicity 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 booste r 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 ty pe-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 chimpanze e responded with a low-titered type-specific neutralizing antibody res ponse 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 contra st, the Env subunit vaccine boosted cellular but not humoral immune re sponses. In the second phase of the vaccination protocol, both virus s hedding and anti-adenovirus responses were enhanced. All three chimpan zees responded to the intranasal administration of Ad7-HIVs with boost ed anti-HIV serum responses, including low-titered type-specific neutr alizing antibodies, elicited anti-HIV antibodies at secretory sites, a nd stimulated cell-mediated immune responses to both Gag and Env antig ens.