Vaccine-induced antibodies to the native, oligomeric envelope glycoproteins of primary HIV-1 isolates.

A simple and sensitive method for measuring antibodies to primary human immunodeficiency virus type 1 (HIV-1) isolates has been developed. The flow cytometric immuno-fluorescence assay detects antibodies that bind to the native, oligomeric form of the envelope glycoprotein (gp120) expressed on the surface of PM-1 cells infected with primary isolates of HIV-1. Sera from people infected with HIV-1 or those immunized with recombinant gp120 vaccines were tested. Significant correlation was observed between neutralizing activity and oligomeric gp120 binding activity. Thirteen to 100% of individuals immunized with the subtype B bivalent vaccine AIDSVAX B/B developed oligomeric gp120 binding antibodies against a variety of subtype B primary isolates. For several isolates, AIDSVAX B/B sera reacted better than monovalent AIDSVAX B sera, suggesting that addition of the second immunogen improved the breadth of the antibody response. Cross-subtype binding activities, induced by AIDSVAX B/B, were lower than activities to subtype B isolates, suggesting that additional immunogen(s) may be desirable in vaccine(s) formulated for geographic regions where non-B subtypes are dominant.

Derivation of herpesvirus saimiri-transformed CD8+ T cell lines with noncytotoxic anti-HIV activity.

Herpesvirus saimiri (HVS), strain 488-77, was used to derive continuously growing transformed human CD8+ T cell lines that can suppress HIV replication in CD4+ cells via the production of an antiviral factor(s). Transformed CD8+ cell lines were obtained by HVS infection of peripheral blood mononuclear cells or purified CD8- T cells from HIV-infected or uninfected individuals. Suppression of primary or laboratory isolates of HIV was mediated by factor permeation of a transwell membrane or by cell-free culture supernatants. Suppressing and nonsuppressing cell lines were IL-2-dependent for good growth and showed a similar activated cell surface phenotype. The cell lines produced varying amounts of the cytokines IL-8, IL-10, TNF-alpha, TNF-beta, RANTES, MIP-1 alpha, and MIP-1 beta, but not IFN-alpha. No correlation was observed between the level of any of these cytokines and the presence or absence of antiviral activity in cell line culture supernatants. These cell lines have become an important resource for studying antiviral factors produced by CD8+ T cells from HIV-infected individuals.