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Viral Envelopes: Structure-Function Studies
Monday, 1:30 - 3:30 pm
Background: Studies that examine the genetic and antigenic properties of HIV-1 isolates reveal that genetic diversity does not parallel antigenic diversity and that HIV-1 strains from different geographic regions can be grouped into a small number of immunologically defined groups (immunotypes).
Methods: HIV-1 subtype in plasma was determined by sequencing and phylogenetic analysis of the C2V5 region of gp120. The binding patterns of 28 monoclonal antibodies (mAbs) (specific for V3 and C5 of gp120, and cluster I of gp41) with 26 HIV-1 virions obtained globally were determined in a virus binding assay. The binding matrix of these viruses and mAbs were subjected to multivariate analysis to identify a limited number of mAbs that can define HIV-1 immunotypes. The binding patterns of the identified mAbs were then tested with 24 additional viruses of different subtypes and the binding data were again subjected to multivariate analysis to define immunotypes.
Results: HIV-1 subtypes
identified included subtype A, B, D, F, G, H, and CRF02_AG. Analysis of the
binding patterns of the 26 viruses with 28 monoclonal antibodies (728 monoclonal
antibodies/virus combinations) revealed 6 of the 28 monoclonal antibodies that
could correctly immunotype 24 of the 26 isolates (92%) into 3 immunotypes. The 6
monoclonal antibodies identified were directed against epitopes in the V3 and
C5 regions of gp120, as well as cluster I of gp41. The binding patterns
(“profiles”) of these 6 monoclonal antibodies with 24 additional HIV-1 virions
confirmed that epitopes in V3 and C5 of gp120 and cluster I of gp41 are well
exposed on these viruses. Multivariate analysis of the binding patterns of
these 6 monoclonal antibodies with all 50 viruses (26 obtained globally and 24
Conclusions: This study suggests that a vaccine against HIV-1 need not be based on geographic origin of the virus or on genetic subtype, but may better be based on antigenic properties that classify the plethora of different HIV-1 viruses into immunologically defined groups.
Keywords: immunotypes; antigenicity; diversity