Sunday 1 December is World AIDS Day. This remains a very important day, as AIDS is still one of the deadliest diseases in the world. World AIDS Day is a good time to take a closer look at BPRC’s role in AIDS research.
What causes AIDS?
In 1982, a mysterious disease appeared which we would later call AIDS. Scientists discovered that HIV was the cause of AIDS. Chimpanzees were used as the subjects in this initial study. That was necessary, since only humans and chimpanzees were found to be susceptible to HIV infection. Thanks to chimpanzees, we know how HIV spreads throughout the body and we understand how the immune system deals with the virus.
SIV was discovered in 1983. Lesser known to the general public, SIV is an HIV-like virus that infects macaques. Experimental SIV infections provided even more insight into the course of the infection and showed us how smart the virus is in fooling our immune system.
What do we need all this knowledge for?
To develop HIV drugs. The result is that now, 37 years after the discovery of the virus, HIV no longer has to be a death sentence. Unfortunately, the current drugs cannot stop the HIV epidemic. In 2019, around 7,000 people are still infected each day and not everyone in the world has access to the necessary drugs.
How can we treat or prevent HIV?
To stop HIV, we need a vaccine. A vaccine teaches the immune system to recognise a pathogen, so that the culprit can quickly be eliminated as soon as we encounter it in real life. Researchers have been working on an HIV vaccine since the 1980s, but creating an effective vaccine has proven extremely difficult in practice: HIV appears to be ‘smarter’ than most other viruses and has developed numerous ways to bypass the immune system.
Still, there is hope. During the rise of HIV, scientists discovered its molecular biology. This knowledge led to techniques that were used to ‘coat’ SIV with HIV, for example, giving rise to artificial viruses that we call SHIV. Thanks to SHIV, we can now test new vaccines on macaques. Such testing is necessary, since no matter how good a theoretical idea may be, the protective effect of an HIV vaccine depends on numerous (unknown) factors.
How do we know whether a vaccine works?
The actual effect of a vaccine can only be tested in living organisms, such as humans and animals. Before a drug can be tested on humans, it must first be tested on animals (in accordance with the law). Many vaccines work based on specific antibodies. When a small amount of a virus is injected, the immune system recognises it as foreign to the body. The immune system then starts making antibodies that will protect the body as soon as the real virus is encountered. But to provide protection against HIV, we need more than just antibodies.
How do we test the effectiveness of an HIV vaccine?
Two things are needed: a well-functioning immune system and an animal model that is susceptible to the infection. To test a vaccine, we vaccinate monkeys (macaques). The animals are typically given three vaccinations spaced a few weeks apart. Around two weeks after each vaccination, we draw blood. That blood goes to the lab for analysis. BPRC uses various techniques to test whether the vaccine has had the desired effect. For example, in addition to examining the blood for the presence of antibodies and T-cells, we assess the functionality of these elements as well.
BPRC has studied numerous HIV vaccines over the past several decades. A number of these are being developed elsewhere in the scientific community for human use, but thus far no one has been able to create a truly effective HIV vaccine.
Search for alternatives to animal testing
BPRC works according to the principles of the three Rs: replacement, reduction and refinement of experiments involving animal testing. In the context of our research on HIV/AIDS, this translates into the following for each ‘R’:
Replacement: groundbreaking developments
HIV/SIV research has been groundbreaking for the entire biomedical field. It has led to many new – mostly in vitro (a biological technique applied outside of the body of an organism) – animal-free research methods used by diagnostic and research laboratories all over the world. Because HIV can only infect humans and chimpanzees, for a long time there was no other option than to study the effect of vaccines in chimpanzees. With the development of SHIV, it is now possible to conduct this research with macaques, meaning chimpanzees are no longer needed. Unfortunately, there is still no replacement method for studying the complex interaction between a vaccine and a virus in the immune system.
Reduction: better vaccines possible in theory
It is theoretically possible to design better HIV vaccines, thanks to the vast knowledge available worldwide. Several of the initial vaccines would probably no longer be tested on animals now, for example because these models show that they would not produce enough antibodies or cytotoxic T-cells.
Refinement: progress in technology and animal welfare
The rise of HIV and the unprecedented progress in biomedical science go hand in hand, in terms of both technology and animal welfare. As a result, much more data can be collected per animal and their discomfort can in turn be minimised.
Would you like to know more about our research on HIV/AIDS and other serious diseases? Read more about our research areas.