CaltechAUTHORS
Published October 8, 2013 | Version Published + Supplemental Material
Journal Article Open

HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice

Creators

  • 1. ROR icon University of Pennsylvania
  • 2. ROR icon Institut Pasteur
  • 3. ROR icon University of Cologne
  • 4. ROR icon Beth Israel Deaconess Medical Center
  • 5. ROR icon Princeton University
  • 6. ROR icon California Institute of Technology
  • 7. ROR icon Rockefeller University

Abstract

Effective control of HIV-1 infection in humans is achieved using combinations of antiretroviral therapy (ART) drugs. In humanized mice (hu-mice), control of viremia can be achieved using either ART or by immunotherapy using combinations of broadly neutralizing antibodies (bNAbs). Here we show that treatment of HIV-1–infected hu-mice with a combination of three highly potent bNAbs not only resulted in complete viremic control but also led to a reduction in cell-associated HIV-1 DNA. Moreover, lowering the initial viral load by coadministration of ART and immunotherapy enabled prolonged viremic control by a single bNAb after ART was withdrawn. Similarly, a single injection of adeno-associated virus directing expression of one bNAb produced durable viremic control after ART was terminated. We conclude that immunotherapy reduces plasma viral load and cell-associated HIV-1 DNA and that decreasing the initial viral load enables single bNAbs to control viremia in hu-mice.

Additional Information

© 2013 National Academy of Sciences. Contributed by Michel C. Nussenzweig, August 14, 2013 (sent for review July 30, 2013. Published online before print September 16, 2013. We thank Caroline Eden for protein production and immunoassays; Alexander Abadir, Han Gao, and Xiying Fan for protein production; and Reha-Baris Incesu for hu-mouse screening. We thank Marcus Dorner, Eva Billerbeck, Rachael N. Labitt, Chase Budell, Tamar Friling, Kevin Vega, and Brenna Flatley for assistance with hu-mouse production. F.K. was supported by the Stavros Niarchos Foundation. E.B., M.D., A.P., and C.M.R. were supported by the Starr Foundation. O.S. is supported by grants from the Agence Nationale de Recherche sur le Sida, Sidaction, AREVA Foundation, Vaccine Research Institute, the Labex Integrative Biology of Emerging Infectious Diseases program, the Seventh Framework Programme HIT Hidden HIV (Health-F3-2012-305762), and Institut Pasteur. This work was supported in part by the Bill and Melinda Gates Foundation with Comprehensive Antibody Vaccine Immune Monitoring Consortium Grant 1032144 (to M.S.S.) and Collaboration for AIDS Vaccine Discovery Grants 38660 (to P.J.B.) and 38619s (to M.C.N.). This work was also supported by the German Center for Infection Research (S.G. and H.B.), UL1 TR000043 Translational Science Award (Clinical and Translational Science Award) program, AI 100663-01 (to M.C.N.), Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, and AI 100148-01 (to P.J.B. and M.C.N.). P.J.B. and M.C.N. are Howard Hughes Medical Institute Investigators. Author contributions: J.A.H., O.S., P.J.B., F.K., and M.C.N. designed research; J.A.H., A.H.-S., H.M., A.D.G., T.R.E., M.M., E.B., M.D., E.K., R.K., M.S.S., and F.K. performed research; A.T., S.G., H.B., J.M.W., C.M.R., and A.P. contributed new reagents/analytic tools; J.A.H., A.H.-S., F.K., and M.C.N. analyzed data; and J.A.H. and M.C.N. wrote the paper. The authors declare no conflict of interest.

Attached Files

Published - PNAS-2013-Horwitz-16538-43.pdf

Supplemental Material - pnas.201315295SI.pdf

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Additional details

Identifiers

PMCID
PMC3799352
Eprint ID
42247
Resolver ID
CaltechAUTHORS:20131105-095202612

Funding

Stavros Niarchos Foundation
Starr Foundation
Agence Nationale de Recherche sur le Sida
Sidaction
AREVA Foundation
Vaccine Research Institute
Labex Integrative Biology of Emerging Infectious Diseases program
Seventh Framework Programme HIT Hidden HIV
Health-F3-2012-305762
Institut Pasteur
Bill and Melinda Gates Foundation
1032144
Collaboration for AIDS Vaccine Discovery
38660
Collaboration for AIDS Vaccine Discovery
38619s
German Center for Infection Research
UL1 TR000043
NIH
AI 100663-01
NIH
AI 100148-01

Dates

Created
2013-11-06
Created from EPrint's datestamp field
Updated
2021-11-10
Created from EPrint's last_modified field