03 Jan 07

Bigger is not necessarily better when it comes to an immune response against HIV, according to research published in Nature Medicine by Oxford University, Harvard Medical School and the University of KwaZulu-Natal, South Africa. The finding has important implications for the development of a vaccine against the disease.

Professor Philip Goulder from Oxford's Department of Paediatrics and Peter Medawar Building for Pathogen Research said: 'Conventional medical wisdom tells us that the bigger the immune response, the more effective it will be in controlling HIV. However, our study suggests that this might not be the case. While most of the immune responses generated against HIV appear to be ineffective, responses targeting one particular HIV protein can bring about control of the virus.'

The research, funded by the Wellcome Trust in the UK and the National Institutes of Health in the US, investigated the immune responses against HIV in nearly 580 HIV-infected people in KwaZulu-Natal, South Africa.

When HIV infects the body, it hides out in so-called 'helper T cells'. T cells play an important role in the immune response generated by the body to fight infection. There are a number of different types of T cells, each playing a different role in this battle. Helper T cells (HTCs) regulate the body's immune response and it is the loss of these cells that leads to the development of AIDS. Another type of T cell, the cytotoxic T cell (CTC), recognises and attacks infected HTCs.

It was previously thought that the bigger the CTC response, the more effective it would be. It is this dogma that has influenced development of HIV vaccines, with vaccines attempting to stimulate a large response.

However, Professor Goulder and colleagues found that the type of CTC response is crucial and that some types of response could actually hinder the immune response.

'Some of these T cells attack so-called Gag proteins within the HIV virus, whilst others attack proteins such as the Env protein on its surface,' explained Professor Goulder. 'In our study group, it seems that the higher the response to the Gag proteins, the more effective the immune system was at fighting infection. However, for reasons that are unclear, the opposite was true for responses to the Env proteins, where a stronger response was associated with a higher viral load - in other words, worse control of HIV.'

About 40 million people are thought to be living with HIV worldwide. The virus, which causes AIDS, is thought to kill 3 million people each year. Despite being first identified in 1981, a vaccine to prevent infection has so far proved elusive. Professor Goulder believes these findings may have implications for the development of a HIV vaccine. 'There seems to be clear evidence that Gag is good,' he said. 'This means that rather than developing a vaccine with a spectrum of CTC responses, we may need to look at a more targeted vaccine.'