The Effectiveness of Human Antibodies in Influencing an AIDS-Like Disease in Monkeys
The purpose of this study is to see if an investigational vaccine can make antibodies (proteins found in blood) in humans that will influence the course of an AIDS-like disease in monkeys. Hopefully, the results of this study can be applied to humans.
AIDS, which is caused by infection with HIV, is associated with many deaths and occurrences of disease. Although recent advances have been made in anti-HIV therapy for AIDS, there is no cure for HIV infection or AIDS, and drug therapy is too expensive for most infected populations. Some organizations are trying to make safe and effective vaccines that may prevent HIV infection and AIDS worldwide. Certain vaccines can generate specific antibodies in humans, but they do not inhibit HIV infection in laboratory tests. It is possible, however, that these antibodies may make HIV disease less severe following infection. For this reason, monkeys will be used to evaluate the role of specific human antibodies.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Primary Purpose: Prevention
|Official Title:||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|
|Study Completion Date:||May 2005|
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.
Part II: Juvenile rhesus macaques are divided into 4 groups and are infused with IgG from human participants of Groups I and II at Day 0. At Day 1, the macaques are exposed to SHIV-89.6P. At Days 3, 7, 10, and weekly up to Day 73, the CD4 lymphocyte count, plasma viremia, and antibodies of the macaques are measured.
|Study Chair:||Tom Evans|
|Study Chair:||Sharon Frey|