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New Possibilities discovered for HIV Vaccine Design

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HIV

HIV (Human Immunodeficiency virus) is a lentivirus which forms part of a family of viruses called the retroviruses. Retroviruses replicate using a reverse transcriptase to produce DNA from their RNA genome. The presence of the virus in humans lead to AIDS (Acquired Immunodeficiency Syndrome).

The acute HIV infection does not cause the person much of a problem and is commonly accompanied only by mild flu-like symptoms and consequently often goes undiagnosed at this stage. Viruses can only replicate within the host cells as they require the host's replication machinery in order to replicate. The particular cell that HIV invades are a type of immune cell called CD4+ T cells. They replicate rapidly and a large concentration of the virus is found in the blood. As they replicate they destroy the CD4+ cells. In order to try and combat the infection another type of immune cell called CD8+ T cells increase and the levels in the blood reduce. This is then called the latency stage which can last from weeks to years. During this period the immune system keeps the levels of virus in the blood low, although it can never completely remove it.

The final stage of infection is AIDS itself. At this stage the virus has destroyed so many CD4+ T cells that the body's ability to fight infection is considerably reduced. These cells normally have a role in assisting and directing other immune cells and they are absolutely essential for the functioning of the immune system as a whole. At this stage a person infected with HIV might notice a fairly significant weight loss, recurrent respiratory infections and ulcers etc. These then lead on to more serious opportunistic infections such as tuberculosis and pneumonia which are often fatal.

HIV is spread by three main transmission methods. The first, and most common, is through unprotected sexual relations whereby infected sexual secretions cross into the uninfected person's blood across a mucous membrane. The use of condoms can greatly reduce the spread of infection and so their use is being promoted especially in areas of high prevalence. The second method of transmission is by blood or blood products. This can be by open wounds, blood transfusions or by infected reused needles. HIV has therefore been a problem in drug users and needle exchange sites have been set up to try and reduce this spread. The third method of transmission is from mother to child and this can occur in childbirth or by breast feeding. This can be reduced if the mother takes anti-retrovirals and avoids breast feeding.

 

Epidemiology

HIV is thought to have spread from primates to humans in Sub-Saharan Africa at the beginning of the 20th Century. The first cases were recognised in America in the 1980s and from there the virus has spread across the whole world and is now officially classified as a global pandemic.

The number of people living with HIV is approximately 35 million worldwide (2/3rds of which are in Sub-Saharan Africa) and each year there about 2.7 million new infections. Each year an estimated 2.0 million people die from AIDS. There is currently no cure for HIV/AIDS and treatment consists of expensive, but effective, anti-retrovirals (ARVs) which must be taken indefinitely for the sufferer to remain healthy. There are many ongoing global programmes trying to increase the availability of ARVs especially in developing countries where people cannot afford healthcare. A vaccine would lead to a massive breakthrough in the reduction of the disease as it could protect those unexposed, especially children, on whom HIV has taken such a toll.

Vaccine Difficulties

There are many ways that vaccines can work but the basic principle is that the immune system is exposed to harmless form of the pathogen so that antibodies are formed against this and immunity can be built up. Then, when exposed to the actual pathogen the body is prepared and can rapidly destroy the infection. The most common types of vaccines are either killed so that the preparation is no longer infectious, or they are attenuated so that the part of the pathogen that causes disease is removed but it is still recognisable to the immune system. There also other techniques that are becoming increasingly popular which include methods such as conjugating, toxoids or subunits.

HIV is a difficult virus to make a vaccine for many reasons. Usual the vaccine formulated to reflect the natural immunity of the body to combat infection, however, as no one has ever recovered form HIV this has nto been possible. Most vaccines normal work by protecting against the actual disease rather than the infection itself and as HIV remains latent for such a long period this has proved difficult. The two common methods of killed and attenuated are not possible as killed HIV is not immunogenic and attenuated HIV could revert to being infectious and so is not safe.

 

Latest

Scientists associated with the International AIDS Vaccine Initiative (IAVI) have discovered two new antibodies which are found to be effective in disabling the HIV virus. Knowledge of this particular virus vulnerability then provides a new approach to developing a vaccine. They also hope to find other similar sites to which a vaccine could also be targeted. The basis of this discovery came from the understanding that a minority of HIV cases produce broadly neutralising antibodies (bNAb) which are effective across most strains of the virus. The accepted concept is that in order for a vaccine to be effective it would need to induce the production of these antibodies in the body prior to infection. The scientists involved isolated two new antibodies called PG9 and PG16 which are broadly neutralising from donors in Africa. There are only four other known bNAb and these latest two are the first to have been isolated directly from donor blood. The other bNAbs have not been feasible in vaccine design as they bind to areas on the virus that are much less accessible. These new bNAbs are more potent and also target sites on the virus that are much more accessible so are more likely to lead to effective vaccine development. The site they target is also believed to be stable, and so the high mutation rate of HIV will not effect this.

To find out more:

The Times Online
Science Daily

 

TJC Global

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