HIV therapy by a combination of broadly neutralizing antibodies in humanized mice

Florian Klein, Ariel Halper-Stromberg, Joshua A. Horwitz, Henning Gruell, Johannes F. Scheid, Stylianos Bournazos, Hugo Mouquet, Linda A. Spatz, Ron Diskin, Alexander Abadir, Trinity Zang, Marcus Dorner, Eva K. Billerbeck, Rachael N. Labitt, Christian Gaebler, Paola M. Marcovecchio, Reha Baris Incesu, Thomas R. Eisenreich, Paul D. Bieniasz, Michael S. Seaman1Pamela J. Bjorkman, Jeffrey V. Ravetch, Alexander Ploss, Michel C. Nussenzweig

Research output: Contribution to journalLetter

327 Citations (Scopus)

Abstract

Human antibodies to human immunodeficiency virus-1 (HIV-1) can neutralize a broad range of viral isolates in vitro and protect non-human primates against infection. Previous work showed that antibodies exert selective pressure on the virus but escape variants emerge within a short period of time. However, these experiments were performed before the recent discovery of more potent anti-HIV-1 antibodies and their improvement by structure-based design. Here we re-examine passive antibody transfer as a therapeutic modality in HIV-1-infected humanized mice. Although HIV-1 can escape from antibody monotherapy, combinations of broadly neutralizing antibodies can effectively control HIV-1 infection and suppress viral load to levels below detection. Moreover, in contrast to antiretroviral therapy, the longer half-life of antibodies led to control of viraemia for an average of 60days after cessation of therapy. Thus, combinations of potent monoclonal antibodies can effectively control HIV-1 replication in humanized mice, and should be re-examined as a therapeutic modality in HIV-1-infected individuals.

Original languageEnglish (US)
Pages (from-to)118-122
Number of pages5
JournalNature
Volume492
Issue number7427
DOIs
StatePublished - Dec 6 2012
Externally publishedYes

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Neutralizing Antibodies
HIV-1
HIV
Antibodies
Therapeutics
Passive Immunization
Viremia
Virus Diseases
Virus Replication
Viral Load
Primates
Half-Life
Monoclonal Antibodies
Viruses
Infection

ASJC Scopus subject areas

  • General

Cite this

Klein, F., Halper-Stromberg, A., Horwitz, J. A., Gruell, H., Scheid, J. F., Bournazos, S., ... Nussenzweig, M. C. (2012). HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature, 492(7427), 118-122. https://doi.org/10.1038/nature11604

HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. / Klein, Florian; Halper-Stromberg, Ariel; Horwitz, Joshua A.; Gruell, Henning; Scheid, Johannes F.; Bournazos, Stylianos; Mouquet, Hugo; Spatz, Linda A.; Diskin, Ron; Abadir, Alexander; Zang, Trinity; Dorner, Marcus; Billerbeck, Eva K.; Labitt, Rachael N.; Gaebler, Christian; Marcovecchio, Paola M.; Incesu, Reha Baris; Eisenreich, Thomas R.; Bieniasz, Paul D.; Seaman1, Michael S.; Bjorkman, Pamela J.; Ravetch, Jeffrey V.; Ploss, Alexander; Nussenzweig, Michel C.

In: Nature, Vol. 492, No. 7427, 06.12.2012, p. 118-122.

Research output: Contribution to journalLetter

Klein, F, Halper-Stromberg, A, Horwitz, JA, Gruell, H, Scheid, JF, Bournazos, S, Mouquet, H, Spatz, LA, Diskin, R, Abadir, A, Zang, T, Dorner, M, Billerbeck, EK, Labitt, RN, Gaebler, C, Marcovecchio, PM, Incesu, RB, Eisenreich, TR, Bieniasz, PD, Seaman1, MS, Bjorkman, PJ, Ravetch, JV, Ploss, A & Nussenzweig, MC 2012, 'HIV therapy by a combination of broadly neutralizing antibodies in humanized mice', Nature, vol. 492, no. 7427, pp. 118-122. https://doi.org/10.1038/nature11604
Klein F, Halper-Stromberg A, Horwitz JA, Gruell H, Scheid JF, Bournazos S et al. HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature. 2012 Dec 6;492(7427):118-122. https://doi.org/10.1038/nature11604
Klein, Florian ; Halper-Stromberg, Ariel ; Horwitz, Joshua A. ; Gruell, Henning ; Scheid, Johannes F. ; Bournazos, Stylianos ; Mouquet, Hugo ; Spatz, Linda A. ; Diskin, Ron ; Abadir, Alexander ; Zang, Trinity ; Dorner, Marcus ; Billerbeck, Eva K. ; Labitt, Rachael N. ; Gaebler, Christian ; Marcovecchio, Paola M. ; Incesu, Reha Baris ; Eisenreich, Thomas R. ; Bieniasz, Paul D. ; Seaman1, Michael S. ; Bjorkman, Pamela J. ; Ravetch, Jeffrey V. ; Ploss, Alexander ; Nussenzweig, Michel C. / HIV therapy by a combination of broadly neutralizing antibodies in humanized mice. In: Nature. 2012 ; Vol. 492, No. 7427. pp. 118-122.
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