Neutralization of HIV type 1 by alloimmune sera derived from polytransfused patients

Antibodies (Abs) against HLA and other cell surface molecules, which HIV-1 acquires during the budding process at the host cell surface, neutralize HIV-1 in vitro. Macaques were protected against infection by SIV grown in human cells after xenoimmunization with human MHC molecules. Besides the immune responses arising against xenogeneic antigens, the highly polymorphic character of the HLA antigens enables the induction of alloresponses after exposure to allogeneic HLA molecules. Since polytransfused (PT) patients develop alloresponses, including humoral anti-HLA responses, we assumed that sera derived from PT patients may neutralize HIV-1. In a model system two PT sera out of a panel of 12 PT and 6 normal control sera neutralized HIV IIIB in vitro. Neutralizing activity of the PT sera was comparable to the efficacy of anti-HIV sera. The neutralizing capacity coincided with strong IgG reactivity against (HIV-infected) cell lines, which were used for virus production, and recognition of cell-free viral particles. Active human complement enhanced HIV neutralization mediated by the sera. Our results suggest an IgG-mediated neutralization based on recognition of allogeneic HLA molecules expressed on the viral surface. A vaccination strategy based on alloimmunization appears conceivable and requires further investigation.