An Open-Label, Passive Antibody Trial to Assess Efficacy in the Pathogenic SHIV-89.6P Macaque Model of Human Antibodies Generated by a Candidate HIV-1 Vaccine in a Phase I Clinical Trial

AIDS, caused by infection with the human immunodeficiency virus type 1 (HIV-1) is associated with enormous morbidity and mortality worldwide. Although recent advances have been made in antiretroviral therapy for AIDS, there is no cure for HIV infection or AIDS, and drug therapy is too expensive for most infected populations. The development of safe, effective vaccines to prevent HIV infection and AIDS worldwide is a commitment of some health-oriented organizations. A major goal in the effort to design an effective vaccine has been the identification of the immunologic correlates of protective immunity. Non-neutralizing antibodies might possess clinically important anti-HIV activities that remain to be defined and warrant investigation. The role played by antibody with minimal neutralizing activity induced by various HIV vaccination strategies is unknown. It is possible that low-level neutralization or other activities may lead to an improvement or worsening in disease course following infection. For this reason it is proposed that a challenge trial in the rhesus macaque SHIV model be performed, in which the role of such antibodies, which are derived from non-infected human vaccinees, will be evaluated.

This is a 2-part study. Part I involves human participants; Part II involves rhesus macaques.

Part 1: Human participants are divided into 2 groups:

Group I: Participants who previously were enrolled in specific AIDS Vaccine Evaluation Group (AVEG) protocols are immunized with a single dose of the recombinant gp160MN/LAI-2 vaccine in alum (aluminum hydroxide adjuvant) on Day 0 of the study.

Group II: Participants who are vaccine naive receive no immunization. Each participant will have 5 clinic visits during the study. Blood is drawn at each visit for routine testing and immune system check. Sera is drawn from participants for neutralizing antibody determination. Approximately 3 weeks after immunization (Day 18), blood is drawn from participants of both groups for a plasmapheresis procedure in which platelets and plasma are removed. This process is repeated 1 week later. Immunoglobulin G (IgG) is purified from the plasma of vaccinated participants.