A five-year study of HIV infected people is pointing the way for further work towards a vaccine.
Scientists have uncovered a weakness in HIV that enables certain people to produce powerful antibodies against different strains of the virus. The discovery – the result of years of study – has been hailed as a major breakthrough in research towards an HIV vaccine.
"You cannot do this kind of research without a long-term commitment to research," said Dr Salim Abdool Karim, director of the Centre for the Aids Programme of Research in South Africa (Caprisa) and president of the Medical Research Council. "These are not answers that will emerge in the course of doing a study over six months. These are studies that were started back in 2003."
Over the past five years, scientists from leading research institutions across the country involved in the Caprisa consortium have studied how HIV-infected individuals develop powerful antibody responses to the virus.
They discovered that sustained attack from the immune system forces the highly adaptable HI virus to develop a sugar coating on its surface. This creates a point of vulnerability, which can be attacked by broadly neutralising antibodies.
When a person is infected with HIV, the body creates antibodies that attack the strain of HIV they are infected with. But one in five HIV-infected people develop broadly neutralising antibodies which can recognise, and attack, many more strains of HIV.
Broadly neutralising antibodies have only recently been identified but they are largely recognised as being key to finding a vaccine against the virus. The antibodies do not represent a cure – HIV mutates rapidly and finds ways to evade antibodies and "hide" in the body – but they do provide an insight into effective ways to attack the virus.
The broadly neutralising antibodies that were studied here were isolated from blood samples taken from women involved in the data-rich Caprisa 002 and Caprisa 004 trials, carried out in KwaZulu Natal over the past few years.
This allowed scientist to track what happened to the virus from the moment the women were infected, and to see how the virus developed over six or seven years, and so broaden their understanding of both the virus and the antibodies. The antibodies were tested against about 200 strains of HIV from around the world and were found to be able to kill up to 88% of the viruses.
Dr Penny Moore, one of the lead authors of the paper, said the findings may give scientists a new pathway or strategy to make an HIV vaccine. But because the virus can still escape broadly neutralising antibodies, this might only be possible through a process of "sequential vaccination", where a series of slightly different vaccines are administered over a period of time, keeping the immune system one step ahead of the mutating virus, rather than one step behind as is currently the case.
"Because the virus gets there first, the virus always wins," according to Moore. The hope is that a set of sequential vaccines can prevent the virus from ever infecting the patient in the first place.
Professor Lynne Morris, head of Aids research at the National Institute for Communicable Disease, said it would be difficult to put a timeline on the development of a vaccine. "It’s a long process. [Medicines Control Council] approval will probably only happen in 2015. The trial itself will take a few years," she said.
The findings were published in the prestigious journal Nature Medicine on Monday, the result of a collaborative study involving 20 authors, 16 of whom are South African.
But at the heart of the research are two South African women, rare individuals who developed powerful antibody responses to HIV, who came back to the clinics month after month, for years on end, to donate blood for research.
"It’s that support and incredible commitment from these women who came back again and again and again that allowed us to ask these kind of questions," said Moore. Sadly for the women, the presence of the broadly neutralising antibodies did not help them fight off HIV infection.
The first, a 43-year-old woman from Durban, has been on antiretroviral therapy (ART) for the past few years. The mother of four is doing well, and has a low viral load.
The second woman, who comes from the rural village of Vulindlela where the microbicide gel trial was carried out, however, did not fare as well. She started ART about two years ago but was admitted to the specialist TB hospital King George V in Durban after contracting multi-drug resistant TB. She later died of extremely drug resistant TB.
Abdool Karim said that the benefit of the discovery would not be for the women themselves but for others who have not yet acquired the virus.
"It’s very unfortunate that she is no longer with us but her specimens, her virus, continues to enable us to study how she developed this response. She has left, in many ways, a lasting legacy that goes beyond her own life," he said.