Horwitz, Joshua A., Halper-Stromberg, Ariel, Mouquet, Hugo ORCID: 0000-0002-4230-610X, Gitlin, Alexander D., Tretiakova, Anna, Eisenreich, Thomas R., Malbec, Marine, Gravemann, Sophia, Billerbeck, Eva, Dorner, Marcus ORCID: 0000-0003-0321-4226, Buening, Hildegard, Schwartz, Olivier, Knops, Elena, Kaiser, Rolf, Seaman, Michael S., Wilson, James M., Rice, Charles M., Ploss, Alexander ORCID: 0000-0001-9322-7252, Bjorkman, Pamela J., Klein, Florian and Nussenzweig, Michel C. (2013). HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice. Proc. Natl. Acad. Sci. U. S. A., 110 (41). S. 16538 - 16544. WASHINGTON: NATL ACAD SCIENCES. ISSN 0027-8424

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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load by coadministration of ART and immunotherapy enabled prolonged viremic control by a single bNAb after ART was withdrawn.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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Horwitz, Joshua A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Halper-Stromberg, ArielUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mouquet, HugoUNSPECIFIEDorcid.org/0000-0002-4230-610XUNSPECIFIED
Gitlin, Alexander D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tretiakova, AnnaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Eisenreich, Thomas R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Malbec, MarineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gravemann, SophiaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Billerbeck, EvaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dorner, MarcusUNSPECIFIEDorcid.org/0000-0003-0321-4226UNSPECIFIED
Buening, HildegardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schwartz, OlivierUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knops, ElenaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kaiser, RolfUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Seaman, Michael S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wilson, James M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rice, Charles M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ploss, AlexanderUNSPECIFIEDorcid.org/0000-0001-9322-7252UNSPECIFIED
Bjorkman, Pamela J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Klein, FlorianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nussenzweig, Michel C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-474145
DOI: 10.1073/pnas.1315295110
Journal or Publication Title: Proc. Natl. Acad. Sci. U. S. A.
Volume: 110
Number: 41
Page Range: S. 16538 - 16544
Date: 2013
Publisher: NATL ACAD SCIENCES
Place of Publication: WASHINGTON
ISSN: 0027-8424
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
IMMUNODEFICIENCY-VIRUS TYPE-1; PASSIVE TRANSFER; B-CELLS; POTENT; THERAPY; INFECTION; COMBINATION; PROTECTION; REPLICATION; INDIVIDUALSMultiple languages
Multidisciplinary SciencesMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/47414

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