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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