CHIMERIC MACAQUE HUMAN FAB MOLECULES NEUTRALIZE SIMIAN IMMUNODEFICIENCY VIRUS

A collection of simian immunodeficiency virus (SIV) neutralizing recom binant Fab fragments was generated using the combinatorial antibody li brary approach. Functional antibody fragments efficiently expressed in Escherichia coli were identified only in the form of chimeric macaque heavy chain gamma 1 and human light chain kappa. The gamma 1 and kapp a chains were derived from a clinically healthy long-term surviving SI Vsm-infected cynomolgus macaque and from an asymptomatic HIV-2 seropos itive individual, respectively. The combinatorial library was construc ted on the surface of filamentous phage using the pComb3 phagemid vect or and screened against purified SIVsm surface glycoprotein (gp148). T welve chimeric clones reacting with the antigen were isolated. Six of these clones showed a pronounced neutralizing activity against SIVsm w ith effects at concentrations of 0.01-0.1 mu g/ml. AH neutralizing Fab fragments were clonally unrelated as demonstrated by nucleic acid seq uencing. These potent neutralizing reagents will be used for prophylac tic and therapeutic immune intervention of lentivirus infection in mac aques and to map neutralizing determinants of SIV. (C) 1995 Academic P ress, Inc.