Human immunodeficiency virus type 1 (HIV-1)-specific monoclonal antibodies with extraordinary potency and breadth have recently been described. In humanized mice, combinations of monoclonal antibodies have been shown to suppress viraemia, but the therapeutic potential of these monoclonal antibodies has not yet been evaluated in primates with an intact immune system. Here we show that administration of a cocktail of HIV-1-specific monoclonal antibodies, as well as the single glycan-dependent monoclonal antibody PGT121, resulted in a rapid and precipitous decline of plasma viraemia to undetectable levels in rhesus monkeys chronically infected with the pathogenic simian–human immunodeficiency virus SHIV-SF162P3. A single monoclonal antibody infusion afforded up to a 3.1 log decline of plasma viral RNA in 7 days and also reduced proviral DNA in peripheral blood, gastrointestinal mucosa and lymph nodes without the development of viral resistance. Moreover, after monoclonal antibody administration, host Gag-specific T-lymphocyte responses showed improved functionality. Virus rebounded in most animals after a median of 56 days when serum monoclonal antibody titres had declined to undetectable levels, although, notably, a subset of animals maintained long-term virological control in the absence of further monoclonal antibody infusions. These data demonstrate a profound therapeutic effect of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys as well as an impact on host immune responses. Our findings strongly encourage the investigation of monoclonal antibody therapy for HIV-1 in humans.

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  1. 1.

    , , & Broadly neutralizing antibodies present new prospects to counter highly antigenically diverse viruses. Science 337, 183–186 (2012)

  2. 2.

    et al. Antibodies in HIV-1 vaccine development and therapy. Science 341, 1199–1204 (2013)

  3. 3.

    et al. Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 329, 856–861 (2010)

  4. 4.

    et al. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 329, 811–817 (2010)

  5. 5.

    et al. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature 458, 636–640 (2009)

  6. 6.

    et al. Sequence and structural convergence of broad and potent HIV antibodies that mimic CD4 binding. Science 333, 1633–1637 (2011)

  7. 7.

    et al. Increasing the potency and breadth of an HIV antibody by using structure-based rational design. Science 334, 1289–1293 (2011)

  8. 8.

    et al. Broad and potent neutralizing antibodies from an African donor reveal a new HIV-1 vaccine target. Science 326, 285–289 (2009)

  9. 9.

    et al. Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9. Nature 480, 336–343 (2011)

  10. 10.

    et al. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature 477, 466–470 (2011)

  11. 11.

    et al. Broadly neutralizing antibody PGT121 allosterically modulates CD4 binding via recognition of the HIV-1 gp120 V3 base and multiple surrounding glycans. PLoS Pathog. 9, e1003342 (2013)

  12. 12.

    et al. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc. Natl Acad. Sci. USA 109, E3268–E3277 (2012)

  13. 13.

    et al. Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120. Nature Struct. Mol. Biol. 20, 796–803 (2013)

  14. 14.

    et al. Broad and potent neutralization of HIV-1 by a gp41-specific human antibody. Nature 491, 406–412 (2012)

  15. 15.

    et al. Neutralizing antibodies have limited effects on the control of established HIV-1 infection in vivo. Immunity 10, 431–438 (1999)

  16. 16.

    et al. Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies. Nature Med. 11, 615–622 (2005)

  17. 17.

    et al. Adjunctive passive immunotherapy in human immunodeficiency virus type 1-infected individuals treated with antiviral therapy during acute and early infection. J. Virol. 81, 11016–11031 (2007)

  18. 18.

    et al. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature 492, 118–122 (2012)

  19. 19.

    et al. Restricting HIV-1 pathways for escape using rationally designed anti-HIV-1 antibodies. J. Exp. Med. 210, 1235–1249 (2013)

  20. 20.

    et al. Efficient neutralization of primary isolates of HIV-1 by a recombinant human monoclonal antibody. Science 266, 1024–1027 (1994)

  21. 21.

    et al. Computational analysis of anti-HIV-1 antibody neutralization panel data to identify potential functional epitope residues. Proc. Natl Acad. Sci. USA 110, 10598–10603 (2013)

  22. 22.

    Evaluating Neutralizing Antibodies Against HIV, SIV and SHIV in Luciferase Reporter Gene Assays. Current Protocols Immunol (John Wiley & Sons, 2004)

  23. 23.

    et al. Development and homeostasis of T cell memory in rhesus macaque. J. Immunol. 168, 29–43 (2002)

  24. 24.

    et al. Magnitude and phenotype of cellular immune responses elicited by recombinant adenovirus vectors and heterologous prime-boost regimens in rhesus monkeys. J. Virol. 82, 4844–4852 (2008)

  25. 25.

    , , , & Gag-specific cellular immunity determines in vitro viral inhibition and in vivo virologic control following simian immunodeficiency virus challenges of vaccinated rhesus monkeys. J. Virol. 86, 9583–9589 (2012)

  26. 26.

    et al. T-cell vaccination reduces simian immunodeficiency virus levels in semen. J. Virol. 83, 10840–10843 (2009)

  27. 27.

    et al. Durable mucosal simian immunodeficiency virus-specific effector memory T lymphocyte responses elicited by recombinant adenovirus vectors in rhesus monkeys. J. Virol. 85, 11007–11015 (2011)

  28. 28.

    et al. Three distinct phases of HIV-1 RNA decay in treatment-naive patients receiving raltegravir-based antiretroviral therapy: ACTG A5248. J. Infect. Dis. 208, 884–891 (2013)

  29. 29.

    et al. HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice. Proc. Natl Acad. Sci. USA 110, 16538–16543 (2013)

  30. 30.

    et al. A novel, rapid method to detect infectious HIV-1 from plasma of persons infected with HIV-1. J. Virol. Methods 165, 90–96 (2010)

  31. 31.

    et al. Neutralizing polyclonal IgG present during acute infection prevents rapid disease onset in simian-human immunodeficiency virus SHIVSF162P3-infected infant rhesus macaques. J. Virol. 87, 10447–10459 (2013)

  32. 32.

    et al. Passive neutralizing antibody controls SHIV viremia and enhances B cell responses in infant macaques. Nature Med. 16, 1117–1119 (2010)

  33. 33.

    et al. Evidence for persistent, occult infection in neonatal macaques following perinatal transmission of simian-human immunodeficiency virus SF162P3. J. Virol. 81, 822–834 (2007)

  34. 34.

    et al. Macaques infected with a CCR5-tropic simian/human immunodeficiency virus (SHIV) develop broadly reactive anti-HIV neutralizing antibodies. J. Virol. 81, 6402–6411 (2007)

  35. 35.

    et al. Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys. Cell 155, 531–539 (2013)

  36. 36.

    et al. Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys. Nature 482, 89–93 (2012)

  37. 37.

    et al. Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys. Nature 457, 87–91 (2009)

  38. 38.

    et al. Generation of the pathogenic R5-tropic simian/human immunodeficiency virus SHIVAD8 by serial passaging in rhesus macaques. J. Virol. 84, 4769–4781 (2010)

  39. 39.

    et al. Pathogenicity and mucosal transmissibility of the R5-tropic simian/human immunodeficiency virus SHIV(AD8) in rhesus macaques: implications for use in vaccine studies. J. Virol. 86, 8516–8526 (2012)

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We thank A. Brinkman, M. Ferguson, C. Gittens, R. Geleziunas, R. Hamel, K. Kelly, J. Kramer, A. McNally, D. Montefiori, L. Nogueira, L. Parenteau, M. Pensiero, L. Peter, M. Shetty, D. Sok, K. Stanley, F. Stephens, W. Wagner, B. Walker, A. West and J. Yalley-Ogunro for advice, assistance and reagents. The SIVmac239 Gag peptide pool was obtained from the NIH AIDS Research and Reference Reagent Program. We acknowledge support from the National Institutes of Health (AI055332, AI060354, AI078526, AI084794, AI095985, AI096040, AI10063, AI100148, AI100663); the Bill and Melinda Gates Foundation (OPP1033091, OPP1033115, OPP1040741, OPP1040753); the Ragon Institute of MGH, MIT, and Harvard; the Lundbeck Foundation; and the Stavros Niarchos Foundation. M.C.N. is a Howard Hughes Medical Institute investigator. M.C.N. and D.R.B. are co-inventors on patents covering the monoclonal antibodies used in the present study.

Author information

Author notes

    • Michel C. Nussenzweig
    •  & Dennis R. Burton

    These authors contributed equally to this work.


  1. Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA

    • Dan H. Barouch
    • , James B. Whitney
    • , Jinyan Liu
    • , Kathryn E. Stephenson
    • , Hui-Wen Chang
    • , Joseph P. Nkolola
    • , Michael S. Seaman
    • , Kaitlin M. Smith
    • , Erica N. Borducchi
    • , Crystal Cabral
    • , Jeffrey Y. Smith
    • , Stephen Blackmore
    • , Srisowmya Sanisetty
    •  & James R. Perry
  2. Ragon Institute of MGH, MIT, and Harvard, Cambridge, Massachusetts 02139, USA

    • Dan H. Barouch
    • , Arup K. Chakraborty
    •  & Dennis R. Burton
  3. The Scripps Research Institute, La Jolla, California 92037, USA

    • Brian Moldt
    • , Pascal Poignard
    •  & Dennis R. Burton
  4. The Rockefeller University, New York, New York 10065, USA

    • Florian Klein
    • , Thiago Y. Oliveira
    •  & Michel C. Nussenzweig
  5. Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA

    • Karthik Shekhar
    • , Sanjana Gupta
    •  & Arup K. Chakraborty
  6. New England Primate Research Center, Southborough, Massachusetts 01776, USA

    • Matthew Beck
  7. Bioqual, Inc., Rockville, Maryland 20852, USA

    • Mark G. Lewis
  8. Alpha Genesis, Inc., Yemassee, South Carolina 29945, USA

    • William Rinaldi
  9. Howard Hughes Medical Institute, New York, New York 10065, USA

    • Michel C. Nussenzweig


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D.H.B., M.C.N. and D.R.B. designed the studies. J.B.W., B.M., F.K., T.Y.O., H.-W.C., S.S. and P.P. led the virological assays. B.M., J.L., K.E.S., M.S.S., K.M.S., E.N.B., C.C., J.Y.S., S.B. and J.R.P. led the immunological assays. K.S., S.G. and A.K.C. led the kinetic analyses. J.B.W., J.P.N., M.B., M.G.L. and W.R. led the monoclonal antibody infusions and clinical care of the rhesus monkeys. D.H.B. led the studies and wrote the paper with all co-authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Dan H. Barouch.

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    Supplementary Data

    This file contains samples used for gp120 Env sequence analysis.

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