Human neutralizing human immunodeficiency virus type 2-specific Fab molecules generated by phage display

A panel of human immunodeficiency virus type 2 (HIV-2)-neutralizing, recomb inant Fab fragments was generated by using the phage display technique. The combinatorial library was derived from an asymptomatic, HIV-2-seropositive individual and constructed on the surface of filamentous phage by using th e pComb3 phagemid vector and then screened against native HIV-2 envelope gl ycoprotein (gp125). Ten of 30 Fab fragments generated displayed strong reac tivity in an ELISA and were therefore selected for further study. Six of th ese possessed neutralizing capacity, with titres varying from 20 to 80 agai nst the homologous HIV-2 strain, and one also had a weak neutralizing capac ity against a heterologous HIV-2 isolate, K135. Sequencing of the heavy cha in CDR3 regions showed that the gp125-specific Fabs represented individual clones. These reagents may be useful for studies on the conformational stru ctures of the HIV-2 envelope antigens and their immunogenicity, which may h elp in vaccine design. Furthermore, the cloned Fab genes may be transformed into whole IgG for eukaryotic expression, and as such used for therapeutic and immunoprophylactic studies in HIV-2-infected macaques and, possibly, f or human immunoprophylaxis against HIV-2.