Essay: HIV and the possibility of a vaccine

HIV has several tricks it uses to avoid being neutralized by antibodies. After it was discovered in 1984 that AIDS was caused by HIV, a major obstacle for making a proper vaccine for the global pandemic had emerged. It was found that HIV reproduces at a very high speed, hastily copying its genetic code each time. Many of the resultant mutants thrive, and the variants display different protein antigens. This mutation can be a slight change in the virus’s shape or structure. Normally, a single antigen with impeccable specificity is targeted by an antibody. The immune system takes only a short amount of time to gear up and start producing HIV-specific antibodies. But even in this short time, the virus is able to alter itself so much that the antibody is not able to recognize the majority of the virus in the body and therefore becomes ineffective. As a result the antibodies are simply unable to keep up with the ever changing virus. Subsequently, neither the response induced by a conventional vaccine nor the natural immune response is effective.
An HIV vaccine would have to outwit hundreds of HIV strains to make a dent in the global epidemic. This was in contrast with the viruses that vaccine makers had to deal with till then. Measles virus, and even polio, an RNA virus like HIV could be derailed with a combination of antigens with just a few distinct strains from the virus. So, researchers had to search for a ‘broadly neutralizing antibody’ or a bNAb that would be able to ‘neutralize’ or render incapable a majority of the 162 divergent HIV strains.
Researchers have closely analyzed the immune responses in HIV-infected individuals at various times during the course of their infection, learn more about the types of antibodies that are produced in response to HIV. It has been found that only a very few of the many different types of HIV specific antibodies that are produced by the human immune system are capable of actually binding to the virus and neutralizing it. These select few antibodies are known as ‘neutralizing antibodies’. And those antibodies which are able to effectively neutralize many different strains of HIV are known as broadly neutralizing antibodies. Only a handful of them have been identified as they are very rare.
The HIV is coated in bulky sugar molecules that act as a shield, effectively blocking the antibodies from reaching their target. This is the reason why there are so few broadly neutralizing antibodies against HIV. The region of the HIV envelope protein’gp120’that antibodies would latch on to is the most heavily protected viral protein scientists have ever studied.
HIV bNAbs emerge from a process called “affinity maturation” in which the B cells first exposed to the virus multiply to produce clones that steadily develop more “affinity” for the invader. Ultimately, the fittest immune response is favoured in this process of mutation and selection. Unlike other antibodies, bNAbs appear to evolve slowly over years, accumulating an unusually high number of mutations’three times as many as other antibodies’which gives them their potency and breadth. The process appears to involve stimulation from different epitopes at different points in time. These antibodies have to make more mutations as the virus keeps changing over time.
Most mutations that give bNAbs their powers take place at the tips of the Y-shaped antibody molecules. bNAbs have also evolved to become stickier than other antibodies. This is a response to one of HIV’s features. The gp120 molecules studding HIV’s surface form clusters of three called trimers. Each HIV has only about 10 trimers on its surface, which is very less as compared to other viruses. The antibodies are able to tightly bind to a virus when each arm of the Y can separately grab a different trimer. This dearth of trimers hampers antibodies in case of HIV. But the extra-sticky bNAbs can compensate by latching on to lipids that make up the HIV membrane or even to sugars that coat gp120.
There are other features as well that help the HIV bNAb to hinder the progress of the virus. The loops at the tips of the antibody arms are often extra-long, increasing their ability to catch an epitope.
bNAbs have brought a level of hope and common purpose that this field of research has rarely witnessed. But years of further testing is still required to provide a vaccine that will be able to completely stop this pandemic.