The search for a HIV vaccine has been going on for the last 26 years with very few developments. The disease has grown to be a global pandemic and is one of the biggest killers worldwide today. A very exciting new development has been that two previously unsuccessful vaccines, when used together in a clinical trial, were shown to reduce the risk of HIV infection by about 30%. This has given the industry new hope that they will one day reach an effective solution although this may still be a long way off.
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 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 and the particular cell that HIV invades are CD4+ T cells (immune cells) which are involved in assisting and directing other immune cells. Upon replication the cells are destroyed. Other immune cells, particularly CD8+ T cells then increase and reduce levels of the virus in the blood leading to a symptomless 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. 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.
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.
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. Usually 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 not 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.
Recent Vaccine Success
A recent clinical trial carried out by the US military and Thai Government on 16,000 participants has shown that a combination of two vaccines called RV144 could lead to a reduction in the risk of HIV infection by about a third.
The study involved volunteers in Thailand, half of whom were given a placebo, the other half were given a combination of two candidate vaccines known as Alvac and Aidsvax. The vaccine strategy was prime boost which has been shown to be the most effective for HIV as a single exposure is not enough for a sustained immune response. With prime boost the same antigen is given twice but in two different vectors. The first vaccine ‘primes’ the immune system, while the second ‘boosts’ the response. Both vaccines had been tested previously but only when used individually and neither had shown any significant effects in protecting against HIV. Alvac uses a bird virus canarypox as a vector for 3 genes from the HIV virus. Aidsvax contains a genetically engineered protein from the surface of the HIV virus.
The results, although far from being conclusive, have still been the biggest advance seen in the search for a HIV vaccine in 26 years. The trial started in 2003 with HIV negative people aged 18-30. The group that were given the placebo showed 74 new infections while the group given the vaccines only 51 new infections.
The downside to this particular vaccine is that it has been shown to only be effective against particular strains of the virus; E and B. E is prevalent in South-East Asia while B is found mostly in Europe and the USA. This means that there is little hope for it being effective in Africa, where the burden of disease and new infection is still highest.
Although, this is seen as a great advance in terms of the science behind vaccine design there are concerns as to the public health dilemma that this could incur. Due to the way that HIV spreads often through unprotected sex and needle sharing there is a possibility that those who are vaccinated could decide to take part in more risky behaviour and there is a chance that this could outweigh the 30% reduction in infection risk and cause an even greater increase in the number of new infections rather than reducing them.
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