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Resources » Articles/Knowledge Sharing » Health »
Development of HIV vaccine and its limitation
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There has been numerous preventive programs, many programs by Government and even by NGO,s but inspite of these preventive programs, the HIV epidemics continues to spread throughout the world. WHO and UNAIDS estimated that at the end of 2008, the total number of people living with HIV/AIDS was approximately 75 millions. About 5 millions new cases are detected each year, thus it is clear that there is a desperate need for a preventive vaccine, but even a partially effective vaccine would have significant impact on the worldwide spread of the virus.
Target of HIV vaccine and its development
HIV subverts complement-mediated lysis in two ways :
1. It acquires the host membrane-bound complement control molecules DAF and CD 59 when it buds from host cells.
2. A site on the viral glycoprotein gp41 binds the soluble complement control molecule, factor H (CFH).
Based on these facts, they suggest that the factor H-biding site on HIV might be an appropriate site for directing protective abntibodies. The idea is to stimulate the formation of antibodies that have this site specificity. As a result, HIV will, theoritically not be able to down regulate complement and will be destroyed. This approach could possibly be augmented by antibodies which are specific to the DAF and CD59 molecules on the surface of the resistant HIV. However, it is not clear how such antibodies would avoid targeting host cells.
An advantage to this type of strategy is that protective antibodies could be use to passively immunize those already infected. As opposed to active immunization which stimulates an immune response.
The theory is backed up by some laboratory data. In one study, an antibody which neutralize a number of different lab stains of HIV-1 was found to bind to a site on gp41. This site was conserved in 72% of studied isolates an important copnsideration in the development of a vaccine to the highly variable HIV. Although this study did not target the CFH biding sites mentioned above, it does demonstrate the general feasibility of such an approach.
Limitations for developmet of HIV vaccine
The following are the hurdles the researchers are facig in the development of a vaccine against HIV.
i. Extreme genetic variability of the virus resulting from mutation and recombination.
ii. General lack of understanding of protective immunity against HIV.
iii. Absence of predictive animal models.
iv. Difficulties to implement clinical trials, especially in developing countries like India.
All of these factors impede progress in the search for an effective vaccine. HIV infects cells of the immune system, but can also be detected as free virus. It is therefor recognized that a vaccine should elicit both humoral immunity, which uses the antibodies, to fight the free virus, as well as cellular immunity, which uses the cytotoxic lymphocytes, to kill or control the HIV infected cells. While earlier work has concentrated on vaccines that induce antibodies, now a days efforts are made to reduce both arms of the immune system.
Current status of HIV vaccine
Several candidate vaccine have been developed and are in various stages of preclinical and clinical development. The first clinical trial phase I was performed in the US in 1987. Today more than 30 vaccine candidates have been tested in more than 80 clinical trials including more than 10,000 people. Most trials were done in the US and Europe, but also in developing countries like Cuba, Kenya, Brazil, China, Haiti, Uganda, Thialand and Trininad.
Encouraging result have been obtained usig the "prime boost" approach, in which a canarypox HIV vectored vaccine, which is known to induce considerable cell mediated immunity against HIV infected cells is being reinforced with a follow up dose of recombinant gp 120 subunit vaccine that generates a powerful neutralizing antibody response. A phase III trial started at the end of 2003 in Thialad enrolling more than 16,000 uninfected adults volunteers for the regimen ALVAC -boost gp 120 effectiveness. Several other trials are going on and we yhope that in coming few years we will come up with some potent vaccine which can offer both type of immunity and thus getting rid of this deadly disease called AIDS.
For more details, visit http://dr-healthguide.blogspot.com
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