Case of HIV: War goes on

Before dwelling on HIV virus, it is important to know what it is and how it works. Simply speaking HIV virus is an enveloped RNA virus and belongs to Family Retroviridae. Two enzymes play key role in its replication. First enzyme is reverse transcriptase which transcribes its RNA into DNA within host cell and second enzyme is integrase which helps to integrate this newly transcribed DNA into the host cell DNA and then from onwards it replicates along with host DNA replication.

Its the same virus that leads to the condition of AIDS in which immune system finally fails leading to oppurtunistic infections and cancer and as result of weakened immune system, the patient finally succumbs to infections. The mode of HIV transmission is through body fluids contact. HIV after infection can remain latent for a long time and can become activated by the environment shift.The incubation period varies from few months to upto seven years and even in some cases HIV positive patient never contracts the disease.

Since the discovery of HIV virus back in 1984, the search for its cure or for its vaccine is a never ending struggle and is a constant riddle for the medical community. Scientists obviously have tried every possible method of vaccination but no method so far has bore fruit. The first vaccine that was developed to counter AIDS and was tested in humans was AIDSWAX which proved to be a failure. The vaccine was developed in hope that it will stimulate immune system to develop antibodies against viral envelope but it didn't work because of variable protein character of envelope.

Scientists next thought that they need a vaccine that can produce broadly neutralized antibodies so that it could block viral entry into the host cells. Simply put a type of vaccine that can produce variable type of antibodies in accordance to viral mutation. Though that type of vaccine is still a desirable goal of virologists, researchers settled on a less effective but still acceptable vaccine that might not prevent infection but keep viral count so low that could reduce the chance of getting sick or being able to transmit the disease. That type of vaccine would keep the virus levels very low by inducing Killer T cells that are meant to seek and destroy infected cells thus preventing viral levels to reach their peak which happens in early phase of infection. The maximum level to prevent infection is to keep viral population at 1700 or less viral copies /mm of blood.

Bearing this range in mind, researchers at Merck company developed a vaccine that used adenovirus type 5 as a vector to carry three HIV reserved genes (gag, pol and nef) into the host cells so that they could produce viral proteins and in a sense trick the immune system to produce antibodies against this virus. But this approach failed to produce any significant response in HIV patients. There is no pretending that Merck vaccine failure was a big blow to all active AIDS vaccination search. Scientists considered two probable causes for this vaccine failure. According to them either the choice of reserved genes or choice of virus itself was a wrong decision. The use of common cold virus was a wrong option because since we humans contract this disease on regular basis and have a innate immnue response to this virus in the form of antibodies against common cold. These common cold antibodies might had interfered with the HIV specific Tcell response and might had potentially reduced its effectiveness.

Whatever the reason the Merck vaccine failure caused a lot of pesimism in HIV researchers. Does this means that we have given up? No i guess not yet. So what we have learned so far? What our options are right now?

First precaution is that we have to use dead viruses for vaccination. Using attenuated viruses wiould be the last option because of the danger of viral recombination and also their chance of virulence reversal in viruses. And secondly we have to avoid making vaccines in response to viral envelpe becuse of its variable nature and concentrate on its reserved genome sequences or genes.

In the coming years scientists will concentrate on certain rare individuals which have innate immunity against HIV virus known as elite controllers. These individuals possess such type of genetic mutations that enable them to suppress viral population or don't allow their entry into Tcells. Some of these individuals possess immune cells that have either the greater number or have incresed funtionality. Also certain individuals posses variable CCR5 receptors that block the entry of viruses into WBCs. It is worth mentioning here that a team of German scientists treated a HIV positive person by carrying out a bone marrow transplant of a person by switching his immune cells by the donated bone immune cells of elite controller. The results were astonishing since it wiped out the virus in the HIV positive patient. The results were published in New England Journal of medicine. It is important to remember that HIV virus requires both receptors CD4 and CCR5 to gain entry into host cells. So this trick by nature works on them.
Also it is important to study immune response in monkeys to live attenuated SIV viruses which is a a very strong immune resonse and helps to control the virus. But using a live virus will be avoided in humans because of safety issues. Eventually ideal vaccine will be a broadly neutralising vaccine that could tackle all forms of virus which is still a dream. Details of vaccination research can be seen here.

So far from giving up, scientists are gearing up for yet another assault on this virus. This virus has proved to be tricky and resilient but so are the scientists who are also tenacious and patient. In the end we can hope that eventually we will be able to defeat this virus by our will to live and in time with the magic of Science.