Short Communication: Virion Aggregation by Neutralizing and Nonneutralizing Antibodies to the HIV-1 Envelope Glycoprotein.

We used dynamic light scattering to detect aggregation of HIV-1 virions by antibodies (IgG) to the viral envelope glycoprotein (Env). Virions of different strains were inactivated by 2,2'-dithiodipyridine (AT-2), a procedure that abrogates infectivity but preserves the native antigenic structure of Env. Neutralizing antibodies directed to a V3-base- and glycan-dependent epitope on gp120 and to the apex of the Env trimer, as well as nonneutralizing antibodies to the epitope cluster I on the gp41-ectodomain, aggregated virions, but in markedly narrow concentration ranges. In contrast, the neutralizing antibody 2G12, which is specific for a composite glycan-dependent epitope on gp120 and functionally monovalent because of its unusual domain-swap structure, was nonaggregating. These results have potentially complex implications for vaccine development.