IMMUNOGENICITY OF RECOMBINANT ADENOVIRUS-HUMAN IMMUNODEFICIENCY VIRUS-VACCINES IN CHIMPANZEES FOLLOWING INTRANASAL ADMINISTRATION

Recombinant adenovirus (Ad)-human immunodeficiency virus (HIV) vaccine s expressing HIVIIIB Env and Gag proteins were evaluated for immunogen icity in chimpanzees following intranasal administration. When Ad7-, A d4-, and Ad5-vectored vaccines were administered sequentially at 0, 24 , and 52 weeks, respectively, to three chimpanzees, the inoculations r esulted in limited virus replication in the nasopharynx, but extensive Ad-HIV replication occurred in the intestine. High-titered IgG serum antibody responses to Env and Gag that were nonneutralizing were induc ed following booster administration of Ad4-HIV recombinant viruses. Fo llowing the Ad5-HIV booster, low levels of neutralizing antibodies as well as V3 loop antibodies were induced in all three chimpanzees that persisted for several months. Administration of a gp160 subunit vaccin e (baculovirus derived) in SAF-m 24 weeks later boosted broadly neutra lizing serum antibodies that peaked within 1 month of the injection. T wo additional subunit boosters 19 and 37 weeks later were progressivel y less effective at stimulating serum neutralizing antibody responses. Substantial local immune responses were induced in nasal, vaginal, an d salivary secretions following the third Ad-HIV intranasal immunizati on. These responses were further boosted with the gp160 subunit vaccin e, which also stimulated production of rectal antibodies. The predomin ant responses in all secretions tested were of the IgG isotype, althou gh some IgA responses were also detected. Strong blastogenic responses to HIV recombinant Env and Gag proteins were induced after each immun ization.