In Search of an HIV-AIDS free World : Update-II
Once upon a time, infectious diseases like small-pox, polio happened to be potential threats to the mankind. But, the development of novel vaccines made it possible to fight against those viruses and defeat them. Since AIDS is also caused by HIV, which is a virus, scientists wondered if a vaccine can be developed to have a permanent answer for the disease, thus saving millions of lives around the world. There may be other options like Prostratin which may have a complete cure for AIDS and ground breaking researches are going on in this regard. But as discussed earlier, if a vaccine can be developed to induce an artificial immunity against HIV in the body, undoubtedly the world will be free from AIDS. But the problem is that making any such vaccine is not as easy as it was in the case for other viruses. It is a great challenge for the modern scientists as HIV doesn’t fit into the model of traditional vaccinology.
Why developing HIV vaccine is such a challenge ?
i) Traditional vaccination approach mimics the natural immunity developed by the body after it recovers from the primary attack of the disease. But in the case of HIV-AIDS, not a single patient has been found to have completed full recovery till date.
The Strategy :
ii) Vaccine mainly generates immunity against a particular disease. But HIV is not a disease. It is an infection which can be latent in the host system for several years until it finally develops into AIDS.
iii) While designing a vaccine, it is assumed that the virus for the disease will remain unchanged at its macro molecular i.e the epitope level. So, the immunity developed by the vaccine can induce humoral and/or cell mediated immune response when the virus attacks the host again. But what if the virus keeps changing itself? HIV is such a clever species. It has a high variability in its genome. The rate of HIV replication is about 10^9 per day. This high replication rate along with the high variability can cause a lot of mutation in the resulting progeny viruses and the mutants that successfully evades immunity, gets naturally selected. Different viral coat proteins have been seen from the HIV-1 isolates of the same patient at different times. That is why designing a particular vaccine is a big question.
iv) Vaccines are made from mainly completely killed or live-attenuated organisms. In case of HIV-1, completely killed viruses are inactive i.e. cannot induce immune response whereas the use of live-attenuated viruses have a lot health security risks.
v) Finally before going to a human trial, a vaccine needs to be tested in a model system for number of times to ensure its safety and efficacy. Unfortunately apart from monkey, no such suitable and effective animal model currently exists.
Science is awesome. Scientists are amazing too. Researchers around the world have attempted in their own way to overcome the barriers mentioned above. Most of the AIDS research organizations are trying to develop a vaccine antigen by synthesizing gp 120 or gp 41 which has a comparatively constant structure though the viral coat protein gets mutated. Once HIV attacks and enters in a CD4+ cell, it becomes latent and escapes the immune system. Only if the infected cell produce viral proteins, the immune system can identify and destroy it. So for it to be effective, the immune response of the vaccine must target the virus before entering the cell. The strategy is to look for the viral surface proteins , present outside the host cell, so that before the interaction between gp 120 (and gp41) with CD4 and CXCR4(or CCR5), the immune response can be generated. With this target, scientists have tried to make synthetic gp 120 and gp 41 that can be used as vaccine to induce antibody response in the body. Once an immunity is established, high level of Ab will be generated in response to any further attack and the HIV will be neutralised and cleared from the system.
The Progress: How close are we?
Various research laboratories are following the above mentioned approach to find the answer. But so far, the synthesized gp 120 or gp 41 has not shown stable interaction with the CD4, thus no significant immune response is induced. More than 100 vaccine agents have been tried since 1984, the year in which Dr. Robert Gallo had first identified HIV as the cause of AIDS. In some of the trials, some agents have shown potential to develop vaccines. Others are found to have lot of difficulties in trial processes. Currently, a lot trials are being done both in animal (monkey) as well as the human but there is no such case that has successfully completed all the Phase I, II and III trials. So the journey goes on.
In the NEWS- HIV pioneer Dr. Robert Gallo finally expects to bring AIDS vaccine to clinic:
With reference to the most recent news published in ScienceAlert on 13th Oct. 2015, reports about Dr. Robert Gallo and his team, who after 15years of hard work, at The Institute of Human Virology, Baltimore, Maryland have claimed to have a vaccine agent that will surely give the ultimate answer. They have engineered the gp 120 in such a way that it will interact with the CD4 and get attached with it. But as there is no gp 41, no chance of interaction with CXCR4 or CCR5 occures and thus no G protein coupled signalling pathway is initiated. This stable interaction will lead to a rapid immune response and generation of Ab. That is what is expected for a vaccine to do. Dr. Gallo has declared the start of human trial very soon. We wish he along with his team, get success in this novel approach.
There are many other organization around the world with significant progress.Scientists at the National Institute of Allergy and Infectious Diseases,USA, have made significant progress so far. The researchers at The International AIDS Vaccine Initiative, New York are also working with the same goal. Here is a short video featuring the scientists involved in the project.
This kind of dedication will not go in vain. With such a rapid rate of progress, we hope the world will have a vaccine for AIDS very soon. A day will come when we will wake up from sleep in the morning and realise that the term “HIV-AIDS” was just a nightmare.That day the journey " In Search of an HIV-AIDS free world " will come to an end.
2) Institute of Human Virology, Maryland
3) The International AIDS Vaccine Initiative, New York