3 March 2014
A group of South African scientists, working with scientists from the US, has discovered how a KwaZulu-Natal woman’s body responded to her HIV infection by making potent antibodies – called broadly neutralising antibodies – that could open up new ways of treating and preventing HIV.
Details of the discovery of the antibodies – called broadly neutralising antibodies because they are able to kill multiple strains of HIV from across the world – was published in the prestigious scientific journal Nature on Sunday.
The study describes how the research team found and identified these antibodies in a KwaZulu-Natal woman’s blood and then duplicated them by cloning the antibodies in the laboratory. The cloned antibodies were then used in a series of experiments to elucidate the pathway followed by the woman’s immune system to make these potent antibodies.
The study was conducted by South African researchers in the Caprisa (Centre for the Aids Programme of Research in South Africa) consortium, working jointly with US partners based at the Vaccine Research Center of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, and Columbia University in New York.
Caprisa includes scientists from the National Institute for Communicable Diseases in Johannesburg, the University of KwaZulu-Natal and the University of Cape Town.
‘Hope for future prevention, treatment strategies’
Professor Salim Abdool Karim, leader of the Caprisa consortium, said in a statement on Sunday that the new insights gained from the study into immune responses against HIV “bring hope for future HIV prevention and treatment strategies”, adding that the woman whose antibodies were studied “is doing well on antiretroviral therapy and continues to attend the Caprisa clinic regularly”.
Just over a year ago, the same team of South African researchers reported in Nature Medicine (also part of the Nature group of journals) on their discovery relating to two other KwaZulu-Natal women, that a shift in the position of one sugar molecule on the surface of the HIV virus led to the development of broadly neutralising antibodies against HIV.
Professor Lynn Morris, who leads the research team at South Africa’s National Institute for Communicable Diseases (NICD), commented: “In this new publication we have been able to isolate a broadly neutralising antibody from this Caprisa volunteer and trace its origins to understand exactly how it arose.
“This could lead to new HIV vaccine strategies that are able to stimulate the rare precursors of these protective antibodies,” Morris said.
Antibodies ‘with long arms’
According to Caprisa, all HIV-infected people respond to HIV by making antibodies. While most people’s antibodies are not able to kill (neutralise) a wide range of HIV, a few infected people naturally make antibodies that kill many different kinds of HIV, in other words, broadly neutralising antibodies.
“Broadly neutralising antibodies have some unusual features,” said Dr Penny Moore, one of the lead South African scientists on the study based at the NICD. “The outer covering (envelope) of HIV has a coating of sugars that prevents antibodies from reaching the surface to neutralise the virus. In this patient, we found that her antibodies had ‘long arms’, which enabled them to reach through the sugar coat that protects HIV.”
In their study, the researchers found that these antibodies had “long arms” right at the outset. “We discovered that some HIV antibodies are born with ‘long arms’, requiring less time and fewer changes to become effective in killing HIV,” Moore said.
The identification and successful cloning of these special antibodies has enabled the researchers to make sufficiently large quantities for further testing, similar to the way a medicine used to prevent or treat HIV would be tested.
“Our goal is to test these antibodies, preferably in combination with other broadly neutralising antibodies, directly in patients with HIV infection or in patients at risk of getting infected,” said Karim. “But this will take some time, as the team is currently planning animal studies as a first step. Broadly neutralising antibodies have previously been shown to be effective in preventing and treating HIV infection in animals, but this has never before been shown in humans.”
The future studies on animals and humans are being supported by the Strategic Health Innovation Partnerships, a unit of the South African Medical Research Council, with funding from the Department of Science and Technology.
‘Importance of international scientific partnerships’
Science and Technology Minister Derek Hanekom said in the Caprisa statement that the study “highlights the importance of international scientific partnerships and the contributions of South African researchers to world-class medical science. We are proud of the South African research team who conducted this ground-breaking study, and thank the US partners for their collaboration and support.”
Health Minister Aaron Motsoaledi, announcing the new findings at a press conference in Johannesburg on Monday, said: “We are a step closer to the day where we eventually have a viable vaccine because of what has been announced today.
“This announcement tells us a little more about the HI virus,” Motsoaledi said, adding: “These studies illustrate the importance of research and the need for patience and dedication.
“In 2009, when we unveiled our 10-point programme, number 10 was research and development, and we were worried that research and development in South Africa was taking long in the past decades. But we are very proud that almost every year something is being announced by our scientists in that direction.”
Motsoaledi said his department had more interest in this development than anyone else in the world, as South Africa has the largest burden of HIV infections globally.
He thanked those people living with HIV who had willingly participated in the study. “Your selflessness has been helping the world to better understand the HIV virus so that we can prevent transmission and find the cure.”
The research was primarily funded by the US National Institutes of Health’s Vaccine Research Center and the South African Department of Science and Technology. The South African researchers also have fellowships from the Wellcome Trust, the Fogarty International Center, the National Research Foundation and the Poliomyelitis Research Foundation.