MEDICAL SCIENCE

Intro: In 1983, HIV (human immunodeficiency virus) was found to be the cause of a range of conditions collectively known as AIDS (acquired immune deficiency syndrome). Over 35 million people have since died due to HIV, and the same number live with it.

THE high number of HIV cases and deaths worldwide is in part because the antiretroviral drugs that have been available since the mid-1990s, allowing infections to be managed, are not always widely available in certain parts of the world – namely in Africa, where HIV infection rates are the highest. But also, unlike many other viral diseases, attempts to develop a vaccine for HIV have so far been unsuccessful.

Vaccination against a variety of infectious diseases is now such a routine part of healthcare that it is easy to forget how important it has been in the history of medical science. Many millions of deaths have been prevented since the principles of vaccination were established by the English physician Edward Jenner in the late eighteenth century. Jenner had become aware of local knowledge near his home in Gloucestershire; milkmaids who had previously caught cowpox, a relatively mild disease, did not then suffer from the similar but much more serious, and potentially fatal, smallpox. Jenner conducted trials in which he exposed people to cowpox and some weeks later to smallpox, finding that the more serious and virulent form of the disease did not develop as predicted. It represented the beginning of a long process, which culminated in 1979 when, after a decades-long programme of vaccination, the World Health Organisation (WHO) was able to announce that smallpox had been completely eradicated.

The Success of Vaccines

Great advances in our understanding of how vaccines work was made in the late nineteenth and early twentieth centuries by, among many others, Louis Pasteur, Robert Koch and Paul Ehrlich (the German physician and not the American environmentalist of the same name associated with the study of global population growth). The way in which the immune system works – through the production of antibodies – was discovered, and methods of producing vaccines extended from Jenner’s use of a related mild disease to the use of killed or weakened forms of the original infectious agent, allowing vaccines for a greater range of diseases to be developed. Vaccines were developed for one infectious disease after another, perhaps most famously including the vaccine for polio, developed in 1955 by the American virologist Jonas Salk.

The Trouble With HIV

In among the remarkable successes, vaccines for a few infectious diseases remain frustratingly out of reach. HIV has the ability to evolve quickly, making it difficult to produce a vaccine that will be – and will remain – effective against all the different strains. A further complication arises because it initially evolved to attack the immune system, which has given the virus a complicated surface structure that enables it to evade detection. Vaccines work by stimulating what is known as the adaptive immune system, the part of the system that can remember the structure of pathogens, so that when these are encountered again the immune response will be enhanced. In the case of HIV, the usual ways of producing a vaccine do not work because it is not detected in the first place, so the immune system is not stimulated.

As if the problem of producing a vaccine was not already complicated enough, further difficulties arise because the two usual methods for producing active agents for vaccines have not worked for HIV. Most vaccines have been developed using either a killed or deactivated (attenuated) version of the pathogen, so that it stimulates the immune system without causing harm. HIV that has been killed does not stimulate an immune response, while the complex structure of the virus means that attempting to deactivate it is difficult. Using an attenuated version would run the risk of infecting the patient.

A formidable range of obstacles still exists, but over 30 years of research have provided medical researchers with a huge body of knowledge on HIV, leading many scientists to be optimistic about a future cure. In the meantime, advances in the management of the disease mean that those with HIV, with access to the relevant drugs, can expect to lead an almost normal life. Until a vaccine is found, the challenge remains to extend these treatments to as many people as possible.

Alternative Theories

HIV suppresses the immune system by invading and attacking T cells, which play a crucial role in what is known as cell-mediated immunity. It was thought that, once the virus had invaded a T cell, it replicated and then spread to other T cells through the blood. Recent research has found that it can actually spread much more quickly, by utilising short-lived connections between T cells in order to transfer directly from one cell to another. This may help to explain why those vaccines developed so far have not been very effective, because these have only worked against HIV in the blood, and it may also open up the possibility of new forms of treatment that in some way block this cell-to-cell transmission.

Recommended/Supplementary Reading:

. National Geographic: Ancient “Giant Virus” Revived From Siberian Permafrost