/ 2 March 2014

Clues to curing Aids could live in antibodies

The identification and successful cloning of Caprisa 256's antibodies enables the researchers to make sufficiently large quantities for further testing.
The identification and successful cloning of Caprisa 256's antibodies enables the researchers to make sufficiently large quantities for further testing.

The discovery of how a KwaZulu-Natal woman's body responded to her HIV infection by making potent antibodies may hold the clue to an HIV vaccine or cure for Aids.

In a study that was published in the scientific journal, Nature, on Sunday night, South African and American researchers describe how the research team found and identified these antibodies in her blood, and then duplicated them by cloning the antibodies in a laboratory. The cloned antibodies were used in a series of experiments to elucidate the pathway followed by her immune system to make the antibodies.

The antibodies of the woman, who is referred to as Caprisa 256 in the study, were analysed from six to 225 weeks after infection. "These potent antibodies take years to develop as antibodies constantly evolve. We discovered Caprisa 256's potent antibodies three years after she got infected, so we went backwards in time and traced how they changed over time," said co-author Salim Abdool Karim, who is head of the Centre for the Aids Programme of Research in South Africa (Caprisa).

All HIV infected people respond to the virus by making antibodies. In most patients, these antibodies are not able to kill HIV. However, the immune systems of a few infected people naturally produces antibodies that kill, or neutralise, a wide range of HIV. Such antibodies are called broadly neutralising antibodies.

Virus changes
"Broadly neutralising antibodies have some unusual features. The outer covering, or envelope, of HIV has a coating of sugars that prevents antibodies from reaching the surface to neutralise the virus," said Penny Moore, one of the lead South African scientists on the study based at the National Institute of Communicable Diseases. "In this patient, we found that her antibodies had 'long arms', which enabled them to reach through the sugar coat that protects HIV. We discovered that the antibodies had 'long arms' right at the outset, requiring less time and fewer changes to become effective in killing HIV."

Ironically, Caprisa 256 is on antiretroviral treatment, as her antibodies are unable to kill the HIV in her own body. "When a person develops broadly neutralising antibodies it actually has no benefit to the individual who develops it; [they are] not able to neutralise their own virus," said Abdool Karim. "The reason for that is that it takes several weeks for the antibodies to develop while the virus continues to constantly change. By the time the antibodies become available, they're no longer working for the HIV that exists in the person's body at that time."

Karim said HIV is unusual in the sense that antibodies co-exist with the virus in an infected person's body. "When someone has antibodies against measles, it means they've overcome measles and that their antibodies have destroyed the measles virus. But that is not the case with HIV, as the virus mutates and changes so rapidly." 

The identification and successful cloning of Caprisa 256's antibodies enables 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 those at risk of getting infected," says 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." 

'Bring an end to Aids'
South African researchers who worked on the study under the umbrella of the "Caprisa consortium" include scientists from the National Institute for Communicable Diseases in Johannesburg, as well as the University of KwaZulu-Natal and University of Cape Town. United States-based partners include Columbia University in New York and the Vaccine Research Centre at the National Institute of Allergy and Infectious Diseases.

Health Minister Aaron Motsoaledi was excited about the research under Abdool-Karim's leadership. "Since South Africa has the largest burden of HIV infection globally, we are gratified to see South African scientists undertake this research to find solutions that will bring an end to Aids. We are hopeful that this research will take us one step closer to developing an Aids vaccine," he said.