Unistat : hiv vaccine
reference: http://en.wikipedia.org/wiki/HIV_vaccine
HIV vaccine
From Wikipedia, the free encyclopedia
An HIV vaccine is a hypothetical vaccine against HIV, the etiological agent of AIDS. As there is no known cure for AIDS, the search for a vaccine has become part of the struggle against the disease.
The urgency of the search for a vaccine against HIV stems from the AIDS-related death toll of over 25 million people since 1981.[1] Indeed, in 2002, AIDS became the primary cause of mortality due to an infectious agent in Africa (UNAIDS, 2004).
Alternative medical treatments to a vaccine do exist. Highly active antiretroviral therapy (HAART) has been highly beneficial to many HIV-infected individuals since its introduction in 1996 when the protease inhibitor-based HAART initially became available. HAART allows the stabilisation of the patient’s symptoms and viremia, but they do not cure the patient of HIV, nor of the symptoms of AIDS (Martinez-Picardo et al., 2000). And, importantly, HAART does nothing to prevent the spread of HIV through people with undiagnosed HIV infections. Safer sex measures have also proven insufficient to halt the spread of AIDS in the worst affected countries, despite some success in reducing infection rates.
Therefore, a HIV vaccine is generally considered as the most likely, perhaps the only way by which the AIDS pandemic can be halted. However, after over 20 years of research, HIV-1 remains a difficult target for a vaccine.
Difficulties in developing an HIV vaccine
In 1984, after the confirmation of the etiological agent of AIDS by Prof. Robert Gallo, the United States Health and Human Services Secretary Margaret Heckler declared that a vaccine would be available within two years (Associated Press, 1984). However, the classical vaccination approaches that have been successful in the control of various viral diseases by priming the adaptive immunity to recognise the viral envelope proteins have failed in the case of HIV-1, as the epitopes of the viral envelope are too variable. Furthermore, the functionally important epitopes of the gp120 protein are masked by glycosylation, trimerisation and receptor-induced conformational changes making it difficult to block with neutralising antibodies. In February 2003, Vaxgen announced that their AIDSVAX vaccine was a failure in North America as there was not a statistically significant reduction of HIV infection within the study population (Francis et al., 2003). In November 2003, it also failed clinical trials in Thailand for the same reason. These vaccines both targeted gp120 and were specific for the geographical regions (Billich et al., 2001).
The ineffectiveness of previously developed vaccines primarily stems from two related factors. First, HIV is highly mutable. Because of the virus' ability to rapidly respond to selective pressures imposed by the immune system, the population of virus in an infected individual typically evolves so that it can evade the two major arms of the adaptive immune system; humoral (antibody-mediated) and systemic (mediated by T cells) immunity. Second, HIV isolates are themselves highly variable. HIV can be categorized into multiple clades and subtypes with a high degree of genetic divergence. Therefore, the immune responses raised by any vaccine need to be broad enough to account for this variability. Any vaccine that lacks this breadth is unlikely to be effective.
The typical animal model for vaccine research is the monkey, often the macaque. The monkeys can be infected with SIV or the chimeric SHIV for research purposes. However, the well-proven route of trying to induce neutralizing antibodies by vaccination has stalled because of the great difficulty in stimulating antibodies that neutralise heterologous primary HIV isolates (Poignard et al., 1999). Some vaccines based on the virus envelope have protected chimpanzees or macaques from homologous virus challenge (Berman et al., 1990), but in clinical trials, individuals who were immunised with similar constructs became infected after later exposure to HIV-1 (Connor et al., 1998).
The human body can defend itself against HIV, as work with monoclonal antibodies (MAb) has proven. That certain individuals can be asymptomatic for decades after infection is encouraging.