To identify immunological correlates of protection from HIV infection and/or progression to AIDS using comparative investigations in human and available relevant NHP systems.
Effective vaccination and/or therapeutic intervention to prevent the spread and development of AIDS is likely to require insight into mechanisms of immunological protection from infection and/or disease. Examples of protection from HIV-1 infection are emerging from different clinical as well as preclinical research settings. Vaccine induced protection against HIV-I infection has been demonstrated in chimpanzees, and in the SIV/macaque model. High-risk, exposed humans who remain virus negative appear to have HIV-1 specific cellular immune responses. With respect to disease, progression to AIDS appears to be inhibited in long-term, infected human survivors, and there is a natural resistance to the development of AIDS in infected chimpanzees and in other lentivirus infected African non human primates. Our studies of host-virus relationships may be divided into investigations of (I) - protection from infection (e.g. due to vaccination or repeated low dose exposure); and (II) - protection from disease progression (due to vaccination. immune modulation or natural resistance of the host).
a) Vaccine efficacy trials
-(HIV-I vaccine immunogenicity studies in humans and in chimpanzees in the developed and developing world)
b) Multiple exposure/resistance to infection
- in humans chimpanzees and macaques
II) Disease progression
a) Long term asymptomatics (Natural resistance)
- humans infected with HIV-I and HIV-2
- Chimpanzees infected with HIV-l
- African green monkey infected with SIV
b) Acquired resistance to disease
- immunotherapy / post-exposure vaccination
- infection with attenuated viruses
The specific immune mechanisms to be compared include humoral (neutralising antibodies, lg. isotopes. DACCA) and cellular (Th., NK, CTL) arms of the immune system along with their interactions, as well as the influence of host Major Histocompatibility Complex (MHC) polymorphism's on the immune response. The ultimate goal is to bridge the species barrier between preclinical (NHP) and clinical (human) responses to HIV and to identify immunological mechanisms important for protective immunity. This information will assist the development and evaluation of effective vaccines and therapeutic strategies for the prevention of AIDS.