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MUTATION - October 2005 |
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| AIDS Vaccine-Still a Dream ?? |
| Simit Doshi (7th Sem) |
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”How we fare in the fight against AIDS is crucial. Halting the spread is not only a Millennium Development Goal in itself; it is a prerequisite for reaching most of the others. Only if we meet this challenge can we succeed in our other efforts to build a humane, healthy and equitable world. Let us ensure we are equal to it.” |
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--Kofi Annan, Secretary General, United Nations |
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| The message above clearly justifies that AIDS has become a major health problem globally. Inspite all the efforts it has to be accepted “there is no cure”. We all know that prevention is better than cure BUT we are facing a situation where “Prevention is the only cure”. There are a number of methods of prevention but as we all know, the awareness is lacking. So finally it comes to a point where we need a vaccine to prevent it on a large scale. |
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| WHAT IS THE SEARCH FOR? |
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| HIV Vaccine that induces one or more of the following is being sought: |
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- Broadly neutralizing antibody against HIV primary isolates.
- Cytotoxic T cell responses in a vast majority of recipients.
- Strong mucosal immune responses.
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| At present we have vaccines of mainly 2 kinds : |
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| - Synthetic subunit vaccines e.g. gp120 with an adjuvant - generates more of a humoral response, .used therapeutically along with drugs. the immunity developed helps in reducing drug dosages. |
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- Live vector vaccine using adenovirus or vaccinia virus-generates more of a cellular (CD8) response
At the same time, efforts continue on the lines of developing a comprehensive therapy to cure AIDS. |
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| Types of Experimental HIV Vaccines: |
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- Peptide vaccine: made of tiny pieces of proteins from the HIV virus.
- Recombinant subunit protein vaccine: made of bigger pieces of proteins that are on the surface of the HIV virus. E.g. gp120, gp140, or gp160 produced by genetic engineering.
- Live vector vaccine: non-HIV viruses engineered to carry genes encoding HIV proteins. The genes are inserted into another vector, which carries them into the body’s cells. The genes in turn produce proteins that are normally found on the surface of the HIV virus. This type of vaccine most resembles the HIV virus but is not harmful.
- DNA vaccine: uses copies of a small number of HIV genes which are inserted into pieces of DNA called plasmids. The HIV genes will produce proteins very similar to the ones from real HIV.
- Vaccine combination: uses any two vaccines, one after another, to create a stronger immune response. Often referred to as ”prime-boost strategy.”
- Virus-like particle vaccine (pseudovirion vaccine): a non-infectious HIV look-alike that has one or more, but not all, HIV proteins
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| WHAT IS LACKING? |
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| Problems with the virus |
- High replication rate High turnover
- Error prone replication mutations in the following generations great amount of genetic diversity. The lack of proof-reading mechanisms adds to the diversity.
- Various types of HIV (type 1C in India); vaccine against one doesn’t protect against the other
Problems with the vaccine
- Correlates. The correlates of immune protection are not known i.e. whether cell mediated immunity or humoral immunity renders better protection is unknown.
- Deployment of a vaccine that has shown efficacy in clinical trials - in the absence of concurrent behavioral intervention - could result in a vaccine whose effectiveness proves lower than its efficacy
- HIV pathogenesis. HIV attacks cells of the immune system that are required to mount an effective response against HIV, and once inside the cell, HIV can remain latently integrated in the host genome until the cell becomes activated. Thus, it might not be possible to prevent or eliminate infection completely. A successful vaccine could be one that prevents disease and transmission to others, but does not prevent infection at the individual level.
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| Problems with volunteers and trial implementation |
- All of us. Have we ever considered ourselves as susceptible to AIDS? Never. And will anyone of us ever volunteer for a trial for a HIV vaccine? Not at all.
- Discrimination. Individuals who test positive for HIV on serological assays may suffer discrimination in employment, health insurance, life insurance, immigration, etc. Several multi-component HIV vaccines will induce immune responses that can result in false positive serological testing on standard assays. Volunteers who receive multi-component candidates should be provided access To testing that could distinguish true infection from vaccine-induced seroconversion.
- Training and Infrastructure. Few developing countries have the trained investigators (science, clinical trials, ethics, lab, data management, project management), and infrastructure (clinics, labs, equipment, supplies) in place to conduct vaccine trials.
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| WHERE HAS IT REACHED? |
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| There is at least as much if not more known about the HIV genome as other pathogens for which vaccines have successfully been made. Advances in genomics and micro-array technologies will likely have multiple applications in the field of HIV vaccine development. |
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| Strategies. Scientists take small parts of the HIV virus and alter them in a laboratory to create synthetic copies. The experimental vaccines do not use whole or live HIV. The vaccines cannot cause HIV or AIDS. The vaccines being tested should produce either antibodies or cytotoxic T cells (CTLs) to fight infection. |
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| MOST PROMISING RESULTS |
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| NANNING, Sept. 17 (Xinhuanet) -- Fifteen volunteers were injected with Chinese home made AIDS vaccine Sunday in Nanning, capital of south China’s Guangxi Zhuang Autonomous Region, a signal China’s phase one AIDS vaccine trial test has entered the final phase, The State Food and Drug Administration (SFDA) approved the first clinical phase of the new AIDS vaccine on Nov. 25, 2004. |
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| IN INDIA |
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| The NARI (National AIDS Research Institute),Pune is planning to conduct the Phase I trials. |
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