Development of AAV Vectored Antibody for HIV Therapy

Leidos Biomedical Research, Inc., Frederick MD

Investigators

Abstract

Up to 1980 humanized mice will be used to determine the ability of passive or AAV mediated delivery of 4 different bnAbs to control HIV-1 infection. The VRC will provide the sequences for each of the 4 bnAb heavy and light chains as well as the proteins for use in the passive therapy experiments to the Subcontractor. The objectives of the Statement of Work (SOW) are to: 1/Measure the in vitro neutralization potential of 4 different bnAbs for a tier two isolate (REJO.c), a tier three isolate (TRJO.c), and an outgrown virus from a chronically infected patient. 2/ Determine the concentrations of each antibody necessary to control established HIV replication in the humanized mice model when infected with each of the above HIV-1 strains. 3/ Determine the effect of combinations of these bnAbs on controlling HIV infection in the humanized mice model. 4/ Sequence escape mutations that arise after treatment with either N6, 10E8, PGT121, and PDGM1400 or their combinations in humanized mice. 5/ Test the sensitivity of all of the above mutant viruses to a panel of bNAbs including N6, 10E8, PGT121, and PDGM1400 in vitro.