HIV Vaccines - Accelerating the Development of Preventive HIV Vaccines for the World: Summary Report and Recommendations of an International Meeting

* The nature of the immune response required to prevent HIV diseases: At present, the
methods of HIV clearance following natural exposure have not been demonstrated. By
analogy with other viral diseases, neutralizing antibodies and cytotoxic lymphocytes
responses are thought to be important, but neither has been shown definitively to confer
protection against HIV disease progression in infected individuals.
* The immunoloqical importance of the different sub-types of HIV: The genetic diversity of
the viral sub-types found worldwide is large. At present the immunological importance of
the different sub-types is not known. The WHO Network for HIV Isolation and
Characterization is collecting and analyzing samples from around the world to improve
current understanding of this issue.
* Animal models: There is no readily available reliable animal model of HIV disease. SIV in
monkeys has some potentially important differences from HIV, and HIV infected
chimpanzees do not develop disease.
* Endpoints for vaccine efficacy trials: There is doubt about what endpoints to use for
vaccine efficacy trials owing to the uncertain relationship between surrogate markers of
disease progression (CD4 count, viral burden) and subsequent disease progression, and
the long latency period between infection and development of disease.
Meeting these challenges will provide a major impetus to the development of preventive HIV
vaccines. The meeting participants, however, felt that it was important that product development
work and the clinical trials of candidate vaccines should not be overly delayed by the unsolved
scientific challenges. Vaccine development and the clinical testing of other viral vaccines have
occurred despite the existence of profound scientific challenges and much has been learned from
this work. In the case of HIV, where no good correlates of protection have been identified and
there is no readily available reliable animal model, there is no substitute for scientifically and
ethically sound human trials. While there are certain characteristics of HIV that warrant caution,
the consensus was that new information will rapidly be generated from trials in humans regardless
of whether or not the candidate vaccine was successful in protecting a large percentage of
volunteers.
2.2 Progress in HIV vaccine development
Product development efforts have focused predominantly on three vaccine strategies - peptides
based on key portions of HIV structural proteins, protein subunits based on HIV structural genes,
and live recombinant viral or bacterial vectors that express one or more HIV proteins. In the last
few years over a dozen products have entered Phase I clinical trials (small-scale safety and
immunogenicity trials) (see Table 1) and two products have entered phase II (large scale safety
and immunogenicity trials). The majority of the products currently being tested are based upon
key portions of the HIV envelope protein (gpl160 or gpl120). Products based on a highly
immunogenic portion of the HIV envelope, the V3 loop, as well as products based on recombinant
viral vectors using pox viruses to express the HIV envelope, are also undergoing Phase I clinical
investigations. None of the Phase I trials have demonstrated any problems with safety and in
several trials, virtually all of the volunteers who received a series of injections produced antibodies
capable of neutralizing laboratory strains of HIV. The trials, however, involve small numbers of
volunteers and have a limited time period of observation. The long term side-effects and duration
of immunity remain to be determined.