Important note: Information in this article was accurate in May 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, May 24, 1999
Daniel J. DeNoon, Senior Editor
These immunotypes - each distinguished by unique signature peptide sequences - are different from the familiar genotypic classification of HIV-1 into subtypes or clades.
"There is every reason to believe that an appropriately constructed and delivered polyvalent HIV vaccine will induce a broad protective response," wrote Susan Zolla-Pazner of Veteran's Affairs Medical Center, New York, and colleagues.
"To construct such a vaccine, it is critical to understand, as completely as possible, the antigenic structure of HIV, to establish and identify immunologic classification for HIV, and to choose rationally among the HIV immunotypes the minimum number and types of viruses that will induce the broadest protective responses."
Zolla-Pazner et al. reported their findings in the Journal of Virology ("Immunotyping of Human Immunodeficiency Virus Type 1 (HIV): An Approach to Immunologic Classification of HIV," J Virol 1999 May;73(5):4042-51.
The researchers acknowledged that practical HIV immunotyping likely will require the generation of further data derived from experiments with human sera and/or monoclonal antibodies (MAbs) derived from different clades than those used in the present study or targeted to different epitopes. Nevertheless, their findings pave the way for such studies.
Zolla-Pazner et al. studied the immunochemical reactivities of 1,176 combinations of human MAbs that recognize the V3 region of the HIV-1 envelope. They then used multivariate statistical analysis to analyze the reactivities to 21 MAbs of 50 peptides from HIV-1 clades A through H.
These studies yielded seven groups of peptides. Each group included peptides from at least two different HIV-1 clades. Within these peptide clusters, the researchers were able to identify what they called "signature sequences" - structural motifs characteristic of each of the V3-based immunotypes.
"The need to identify HIV immunotypes is predicated on the fact that vaccines against immunological diverse organisms are composed of components which are representative of the various serotypes that make up a particular family of organisms," they wrote.
"HIV is also an immunologically diverse group of organisms, and it is therefore unlikely that any single form of virus or product from any single form of HIV will induce immunity to all forms of HIV."
To date, it has been assumed that an HIV vaccine will have to include epitopes from several different HIV clades. The VaxGen candidate HIV vaccine currently being tested in Thailand, for example, contains envelope peptides from the genetically defined clades B and E. Fortunately, the current analysis indicates that these two peptides are from different immunotypes.
"Generally, however, HIV genotypes to HIV immunotypes, and therefore the choice of vaccine components based solely on genetically defined clades may be inappropriate," Zolla-Pazner et al. suggested.
This work was supported by National Institutes of Health grants, by the Veterans Administration Research Center for AIDS and HIV Infection, and by the Department of Veterans Affairs.
The corresponding author for this study is Susan Zolla-Pazner, Veterans Affairs Medical Center, Room 18124No, 423 East 23rd St., New York, NY 10010. Phone: (212) 951-3211. Fax: (212) 951-6321. Email: <zollas01@mcrcr6.med.nyu.edu>.
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