HUMAN STUDIES IN THE DEVELOPMENT OF HUMAN-IMMUNODEFICIENCY-VIRUS VACCINES

The safety and immunogenicity of candidate human immunodeficiency virus type 1 (HIV-I) vaccines have been studied in > 1500 healthy, seronegative (HIV-1-uninfected) subjects. HIV-1 envelope proteins, gp160 and gp120, have been the most extensively investigated. A live virus vector construct, vaccinia with insertion of the HIV-1 env gene, has also been studied. HIV-1 candidate vaccines have been well tolerated, with no acute or longer-term serious toxicity. Intramuscular multidose gp120 vaccines induce neutralizing antibodies, lymphoproliferative responses, and anti-HIV-1 CD4 cytotoxic T cell (CTL) activity. Immunization with the vaccinia-env construct, followed by a boost with an envelope protein, also induces neutralizing antibodies, and anti-HIV-l CTL activity (CD8, major histocompatibility complex class I-restricted) has been observed. To date, serum from vaccinees can neutralize laboratory-adapted HIV-1 strains in vitro but not primary isolates; the significance of this observation is unknown. Additional approaches to vaccination against HIV-1 are in development.