Scientists have obtained their first detailed glimpse of a rare antibody, called b12, which is capable of inactivating many different strains of HIV, the virus that causes AIDS. A crystal structure of b12 has been determined by scientists working at the Scripps Research Institute in California and the Glycobiology Institute at Oxford University. It shows that the antibody has a long finger-like region on its surface that is able to penetrate the surface of the HIV virus and prevent it causing disease.
It is hoped that the structure of this region may provide a basis for the design of effective vaccines against the HIV virus.
HIV damages the immune system by binding to special receptors, called CD4 receptors, which are found on the surface of specialized blood cells, such as T cells or macrophages, which defend the body against disease.
The virus infects the cells via the receptors, impairing their function so that patients with HIV become vulnerable to many different infections.
b12 was first identified in the bone marrow of a 31-year-old male who had been HIV positive without symptoms for six years. It is believed to work by binding onto the area of the viral coat which interacts with CD4 receptors, neutralizing it and making the virus unable to invade cells.
While the antibody is rare, its existence demonstrates that the human immune system is capable of raising antibodies that are effective against HIV. Scientists will now be investigating the ways in which this type of immune response can be triggered.
The search for a vaccine against HIV has been made particularly complicated by the fact that there are many subtypes of HIV. The b12 antibody appears to be effective against a wide variety of these isolates, since the region of b12 which binds the virus is shaped so that it can bind most of the viral strains.
The paper, authored by Erica Ollmann Saphire and co-workers under the direction of Ian A. Wilson and Dennis R. Burton, offers a critical template for the design of HIV vaccines.
Dr. Pauline Rudd, a Reader in Glycobiology at the Department of Biochemistry, Oxford University, and Professor Raymond Dwek, Director of the Glycobiology Institute, said, "We are delighted to be collaborating with The Scripps Research Institute on this important project, which will hopefully offer real solutions to the problems of designing an effective virus against AIDS."
The AIDS pandemic is already one of the worst epidemics in recorded history. Some 2.8 million people died of AIDS last year and since the epidemic began, 18.8 million have died of AIDS and there is no sign that the epidemic is slowing.
Overall, there are 24.5 million people infected with HIV in Africa, two thirds of all cases in the world. In the southern African countries, South Africa, Botswana and Namibia, one third of all women attending ante-natal clinics are infected. The figure is similar in some parts of Kenya. In South Africa, there are now more deaths in 30-40 year olds than in 60-70 year olds, a dramatic difference from 1990. The life-time risk of AIDS for a 15-year-old in Botswana is nearly 90%; in Kenya it is 50%.
(Reference: "Crystal Structure of a Neutralizing Human IgG against HIV-1: A Template for Vaccine Design" is published in Science and was authored by Erica Ollmann Saphire, Paul W.H.I Parren, Ralph Pantophlet, Michael B. Zwick, Garrett M. Morris, Robyn Stanfield, Dennis R Burton and Ian A Wilson of The Scripps Research Institute and Pauline M. Rudd and Raymond A. Dwek of the Glycobiology Institute, University of Oxford.)
Related website:
Glycobiology Institute at Oxford University
10-Aug-2001
