SIMIAN IMMUNODEFICIENCY VIRUS (SIV) ENVELOPE-SPECIFIC FABS WITH HIGH-LEVEL HOMOLOGOUS NEUTRALIZING ACTIVITY - RECOVERY FROM A LONG-TERM-NONPROGRESSOR SIV-INFECTED MACAQUE

An antibody phage display library was constructed from RNA extracted f rom lymph node cells of a simian immunodeficiency virus (SIV)-infected long-term-nonprogressor macaque. Seven gp120-reactive Fabs were obtai ned by selection of the library against SIV monomeric gp120. Although each of the Fabs was unique in sequence, there were two distinct group s based on epitope recognition, neutralizing activity in vitro, and mo lecular analysis. Group 1 Fabs did not neutralize SIV and bound to a l inear epitope in the V3 loop of the SIV envelope. In contrast, two of the group 2 Fabs neutralized homologous, neutralization-sensitive SIVs m isolates with high efficiency but failed to neutralize heterologous SIVmac isolates. Based on competition enzyme-linked immunosorbent assa ys with mouse monoclonal antibodies of known specificity, these Fabs r eacted with a conformational epitope that includes domains V3 and V4 o f the SIV envelope. These neutralizing and nonneutralizing Fabs provid e valuable standardized and renewable reagents for studying the role o f antibody in preventing or modifying SIV infection in vivo.