HUMAN-ANTIBODIES FROM PHAGE LIBRARIES - NEUTRALIZING ACTIVITY AGAINSTHUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 EQUALLY IMPROVED AFTER EXPRESSIONAS FAB AND IGG IN MAMMALIAN-CELLS

Human antibodies against HIV-1 have been sought to study neutralizatio n events on the molecular level, and for possible use in passive immun e intervention. The development of phage display techniques has opened the possibility of rapidly generating human monoclonal antibodies wit h desired specificities. We and others have isolated human HIV-1 neutr alizing antibody fragments using this technique. Bacterial expression of isolated clones does, however, differ broadly both in expression le vels and functional activity. In addition, intact IgG cannot be expres sed in bacteria. By transferring the genes of isolated Fab clones to a mammalian expression system we could perform a comparison of function al activity between Fab expressed in bacterial and mammalian cells, as well as Fab and whole IgG. Fab fragments expressed in mammalian cells showed increased virus neutralizing activity compared to the same Fab clones expressed in Escherichia coli, underlining the inefficiency of procaryotic expression. No difference in HIV-1 neutralizing capacity was detected between monovalent (Fab) and divalent (whole antibody) re agents expressed in CHO cells. Thus, bivalency does not always confer improved neutralization efficacy.