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Characterization of a monoclonal anti-capsid antibody that cross-reacts with three major primate lentivirus lineages
Authors:Sanders-Beer Brigitte E  Eschricht Magdalena  Seifried Janna  Hirsch Vanessa M  Allan Jonathan S  Norley Stephen
Affiliation:
  • a BIOQUAL, Inc., 9600 Medical Center Drive, Rockville, MD 20850, USA
  • b Robert-Koch-Institut, Nordufer 20, 13353 Berlin, Germany
  • c Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4 Memorial Dr., Bethesda, MD 20892-0460, USA
  • d Texas Biomedical Research Institute, Department of Virology and Immunology, 7620 NW Loop 410 at Military Drive, San Antonio, TX 78227, USA
  • Abstract:
    Mouse monoclonal antibodies with varying specificities against the Gag capsid of simian and human immunodeficiency virus (SIV/HIV) were generated by immunizing mice with whole inactivated SIVagmTYO-1. Monoclonal antibody AG3.0 showed the broadest reactivity recognizing the Gag capsid protein (p24-27) and Gag precursors p38, p55, and p150 of HIV-1, HIV-2, SIVmac, and SIVagm. Using overlapping peptides, the AG3.0 epitope was mapped in capsid to a sequence (SPRTLNA) conserved among HIV-1, HIV-2, SIVrcm, SIVsm/mac, and SIVagm related viruses. Because of its broad cross-reactivity, AG3.0 was used to develop an antigen capture assay with a lower detection limit of 100 pg/ml HIV-1 Gag p24. Interestingly, AG3.0 was found to have a faster binding on/off rate for SIVagmVer and SIVmac Gag than for SIVagmSab Gag, possibly due to differences outside the SPRTLNA motif. In addition, the ribonucleic acid (RNA) coding for AG3.0 was sequenced to facilitate the development of humanized monoclonal antibodies.
    Keywords:AG3.0   Epitope   Gag   Capsid   p24   p27   Human immunodeficiency virus   Simian immunodeficiency virus
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