Immunoreactivity of intact virions of human immunodeficiency virus type 1 (HIV-1) reveals the existence of fewer HIV-1 immunotypes than genotypes

In order to protect against organisms that exhibit significant genetic vari ation, polyvalent vaccines are needed. Given the extreme variability of hum an immunodeficiency virus type 1 (HIV-1), it is probable that a polyvalent vaccine will also be needed for protection from this virus. However, to und erstand how to construct a polyvalent vaccine, serotypes or immunotypes of HIV must be identified. In the present study, we have examined the immunolo gic relatedness of intact, native HIV-1 primary isolates of group M, clades A to H, with human monoclonal antibodies (MAbs) directed at epitopes in th e V3, C5, and gp41 cluster I regions of the envelope glycoproteins, since t hese regions are well exposed on the virion surface. Multivariate analysis of the binding data revealed three immunotypes of HIV-1 and five MAb groups useful for immunotyping of the viruses. The analysis revealed that there a re fewer immunotypes than genotypes of HIV and that clustering of the isola tes did not correlate with either genotypes, coreceptor usage (CCR5 and CXC R4), or geographic origin of the isolates. Further analysis revealed distin ct MAb groups that bound preferentially to HIV-1 isolates belonging to part icular immunotypes or that bound to all three immunotypes; this demonstrate s that viral immunotypes identified by mathematical analysis are indeed def ined by their immunologic characteristics. In summary, these results indica te (i) that HIV-1 immunotypes can be defined, (ii) that constellations of e pitopes that are conserved among isolates belonging to each individual HIV- 1 immunotype exist and that these distinguish each of the immunotypes, and (iii) that there are also epitopes that are routinely shared by all immunot ypes.