February 5, 2024

Scientists at NHLS achieve breakthrough in HIV research

Two talented young scientists from the National Health Laboratory Service's (NHLS) National Institute for Communicable Diseases (NICD) have made significant strides towards a potential HIV vaccine.
Professor Lynn Morris, who heads the NICD's AIDS Research, and Dr. Penny Moore, a senior scientist in the NICD's Centre for HIV and Sexually Transmitted Infections, played a crucial role in uncovering a vulnerability in the human immunodeficiency virus (HIV) that allows certain individuals to produce potent antibodies capable of neutralizing up to 88% of virus strains worldwide.
The groundbreaking study, conducted by the Centre for the AIDS Programme of Research in South Africa (CAPRISA) consortium, involving researchers from the NICD, University of the Witwatersrand, University of KwaZulu-Natal, University of Cape Town, University of North Carolina, and Harvard University, was published in Nature Medicine.
These scientists have been investigating how some HIV-infected individuals generate robust antibody responses, known as broadly neutralizing antibodies, capable of targeting a wide range of HIV variants. Through their research, they identified two rare cases of women from KwaZulu-Natal, one of whom participated in the CAPRISA 004 tenofovir gel study, who produced these unique antibodies.
Following further investigation into these women, the team, led by Dr. Moore and Professor Morris of NHLS-NICD, discovered that a specific sugar molecule (glycan) at position 332 on the virus's surface protein coat creates a vulnerability site, triggering the body's production of broadly neutralizing antibodies. Analysis of extensive datasets suggests that this phenomenon observed in South African women may also occur in other HIV-infected individuals.
Dr. Moore, a Wellcome Trust Fellow at the NICD, explained, "Understanding this intricate interplay between HIV and the body's immune response has provided valuable insights into the generation of broadly neutralizing antibodies."
Professor Morris elaborated, "We were surprised to find that the virus responsible for infection often lacked this antibody target on its surface. However, over time, immune pressure led the virus to expose this vulnerability, allowing the development of antibodies targeting this weak spot."
Broadly neutralizing antibodies are crucial for the development of an effective AIDS vaccine, as emphasized by Professor Salim Abdool Karim, Director of CAPRISA and President of the Medical Research Council.
While the existence of broadly neutralizing antibodies has been known for some time, highly potent versions were only isolated three years ago. This study sheds light on one mechanism by which these antibodies may be produced. By studying the target of these antibodies, a sugar coating on HIV's surface protein, the research team demonstrated how the virus gradually exposed this vulnerability over time under immune pressure, ultimately enabling the development of broadly neutralizing antibodies.
The CAPRISA consortium, comprising leading AIDS researchers in South Africa and international partners, has dedicated two years to this intensive study. Funding for this research was provided by NHLS, the South African government's Department of Science and Technology, the US National Institutes for Health, and the Bill & Melinda Gates Foundation. Fellowships from the Fogarty International Center and the Wellcome Trust were instrumental in supporting this research.