A number of recent studies have reported the detection of neutralizing antibodies in individuals with chronic HIV infection. In some rare cases, antibody responses capable of neutralizing a broad array of diverse HIV isolates have been documented. In a perspective piece just published by Nature Medicine, Leonidas Stamatatos and colleagues review these findings and suggest that they represent good news for the vaccine field. In particular, they note the data argue that B cells can make antibodies capable of neutralizing HIV; some scientists have been concerned that the antibody structure required to inhibit HIV cannot be created by the human immune system. Based on the new findings, the researchers recommend a series of steps for pursuing structure-based HIV vaccine design:
Figure 1 - Flow chart of structure-based HIV-1 vaccine design.
CREDIT:
Nature Medicine
Published online: 14 June 2009 | doi:10.1038/nm.1949
Neutralizing antibodies generated during natural HIV-1 infection: good news for an HIV-1 vaccine?
Leonidas Stamatatos1,2, Lynn Morris3,4, Dennis R Burton5 & John R Mascola6
1. Seattle Biomedical Research Institute, Seattle, Washington, USA.
2. Department of Global Health, University of Washington, Seattle, Washington, USA.
3. AIDS Virus Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa.
4. Centre for the AIDS Programme of Research in South Africa, Johannesburg, South Africa.
5. Department of Immunology and Microbial Science and the International AIDS Vaccine Initiative Neutralizing Antibody Center, The Scripps Research Institute, La Jolla, California, USA.
6. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA.
Abstract
Most existing viral vaccines generate antibodies that either block initial infection or help eradicate the virus before it can cause disease. For HIV-1, obstacles to eliciting protective neutralizing antibodies (NAbs) have often seemed insurmountable. The target of HIV-specific NAbs, the viral envelope glycoprotein (Env), is highly variable in amino acid sequence and glycosylation pattern. Conserved elements of HIV-1 Env seem to be poorly immunogenic, and previous attempts to generate broadly reactive NAbs by vaccination have proven ineffective. However, recent studies show that antibodies in the sera of some HIV-1–infected individuals can neutralize diverse HIV-1 isolates. Detailed analyses of these sera provide new insights into the viral epitopes targeted by broadly reactive NAbs. The findings discussed here suggest that the natural NAb response to HIV-1 can inform future vaccine design. A concerted effort of structure-based vaccine design will help guide the development of improved antibody-based vaccines for HIV-1.
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