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 from lymph node cells of a simian immunodeficiency virus (SIV)-infected long-term-nonprogressor macaque. Seven gp120-reactive Fabs were obtained by selection of the library against SIV monomeric gp120. Although each of the Fabs was unique in sequence, there were two distinct groups based on epitope recognition, neutralizing activity in vitro, and molecular analysis. Group 1 Fabs did not neutralize SIV and bound to a linear epitope in the V3 loop of the SIV envelope. In contrast, two of the group 2 Fabs neutralized homologous, neutralization-sensitive SIVsm isolates with high efficiency but failed to neutralize heterologous SIVmac isolates. Based on competition enzyme-linked immunosorbent assays with mouse monoclonal antibodies of known specificity, these Fabs reacted with a conformational epitope that includes domains V3 and V4 of the SIV envelope. These neutralizing and nonneutralizing Fabs provide valuable standardized and renewable reagents for studying the role of antibody in preventing or modifying SIV infection in vivo.
Glamann
J
J
Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
Burton
D R
DR
Parren
P W
PW
Ditzel
H J
HJ
Kent
K A
KA
Arnold
C
C
Montefiori
D
D
Hirsch
V M
VM
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral / Q000235:genetics / Q000276:immunology*; D000918:Antibody Specificity; D001483:Base Sequence; D001667:Binding, Competitive; D017931:DNA Primers / Q000235:genetics; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000235:genetics; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D007140:Immunoglobulin Fab Fragments / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D008562:Membrane Glycoproteins; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D014759:Viral Envelope Proteins
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D017931:DNA Primers; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D007140:Immunoglobulin Fab Fragments; D008562:Membrane Glycoproteins; D014759:Viral Envelope Proteins; C069623:gp120 protein, Simian immunodeficiency virus