PRODUCTION AND CHARACTERIZATION OF SIV ENVELOPE-SPECIFIC RHESUS MONOCLONAL-ANTIBODIES FROM A MACAQUE ASYMPTOMATICALLY INFECTED WITH A LIVE SIV VACCINE

Five rhesus monoclonal antibodies (RbMAbs) were produced by rhesus EBV transformation of peripheral blood B cells-from a rhesus macaque that had been:asymptomatically infected with an attenuated, macrophage-tro pic SIV strain, 17E-Cl. These MAbs recognized conformation-dependent e pitopes on SIV gp120 and could not be mapped,using synthetic peptides. All five RhMAbs were able to neutralize the vaccine strain and a hete rologous isolate, SIV/DeltaB670. The RhMAbs did not cross-react with H IV-2; by contrast, four human MAbs derived from an HIV-2-infected pers on were broadly cross-reactive with both SIV and HIV-2 gp120s. Cross-c ompetition analysis indicated that the five RhMAbs could be placed in two groups recognizing:two nonoverlapping epitopes; while-the HMAbs me re placed in two additional competition groups. Binding of the three g roup I RhMAbs (l.7F, 3.11B, and 1.10A) as well as HMAb 17A was shown t o be sensitive to specific amino acid alterations in V4 occurring in n atural env variants; The results of this study demonstrate that RhEBV transformation provides a means to probe rhesus antibody responses to SIV infection at the monoclonal level. RhMAbs will allow structural an d functional studies of envelope glycoprotein determinants that elicit protective immune:responses against SIV.