Universität zu Köln

Gautam, Rajeev, Nishimura, Yoshiaki, Pegu, Amarendra ORCID: 0000-0003-3564-6453, Nason, Martha C., Klein, Florian, Gazumyan, Anna, Golijanin, Jovana, Buckler-White, Alicia, Sadjadpour, Reza, Wang, Keyun, Mankoff, Zachary, Schmidt, Stephen D., Lifson, Jeffrey D., Mascola, John R., Nussenzweig, Michel C. and Martin, Malcolm A. (2016). A single injection of anti-HIV-1 antibodies protects against repeated SHIV challenges. Nature, 533 (7601). S. 105 - 117. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-4687

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Abstract

Despite the success of potent anti-retroviral drugs in controlling human immunodeficiency virus type 1 (HIV-1) infection, little progress has been made in generating an effective HIV-1 vaccine. Although passive transfer of anti-HIV-1 broadly neutralizing antibodies can protect mice or macaques against a single high-dose challenge with HIV or simian/human (SIV/HIV) chimaeric viruses (SHIVs) respectively(1-8), the long-term efficacy of a passive antibody transfer approach for HIV-1 has not been examined. Here we show, on the basis of the relatively long-term protection conferred by hepatitis A immune globulin, the efficacy of a single injection (20 mg kg(-1)) of four anti-HIV-1-neutralizing monoclonal antibodies (VRC01, VRC01-LS, 3BNC117, and 10-1074 (refs 9-12)) in blocking repeated weekly low-dose virus challenges of the clade B SHIVAD8. Compared with control animals, which required two to six challenges (median = 3) for infection, a single broadly neutralizing antibody infusion prevented virus acquisition for up to 23 weekly challenges. This effect depended on antibody potency and half-life. The highest levels of plasma-neutralizing activity and, correspondingly, the longest protection were found in monkeys administered the more potent antibodies 3BNC117 and 10-1074 (median = 13 and 12.5 weeks, respectively). VRC01, which showed lower plasma-neutralizing activity, protected for a shorter time (median = 8 weeks). The introduction of a mutation that extends antibody half-life into the crystallizable fragment (Fc) domain of VRC01 increased median protection from 8 to 14.5 weeks. If administered to populations at high risk of HIV-1 transmission, such an immunoprophylaxis regimen could have a major impact on virus transmission.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gautam, Rajeev UNSPECIFIED UNSPECIFIED UNSPECIFIED Nishimura, Yoshiaki UNSPECIFIED UNSPECIFIED UNSPECIFIED Pegu, Amarendra UNSPECIFIED orcid.org/0000-0003-3564-6453 UNSPECIFIED Nason, Martha C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Gazumyan, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Golijanin, Jovana UNSPECIFIED UNSPECIFIED UNSPECIFIED Buckler-White, Alicia UNSPECIFIED UNSPECIFIED UNSPECIFIED Sadjadpour, Reza UNSPECIFIED UNSPECIFIED UNSPECIFIED Wang, Keyun UNSPECIFIED UNSPECIFIED UNSPECIFIED Mankoff, Zachary UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Stephen D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lifson, Jeffrey D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mascola, John R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nussenzweig, Michel C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, Malcolm A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-275917
DOI:	10.1038/nature17677
Journal or Publication Title:	Nature
Volume:	533
Number:	7601
Page Range:	S. 105 - 117
Date:	2016
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1476-4687
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language SIMIAN/HUMAN IMMUNODEFICIENCY VIRUS; BROADLY NEUTRALIZING ANTIBODY; HIV-1/SIV CHIMERIC VIRUS; MONOCLONAL-ANTIBODIES; IMPROVES PROTECTION; PASSIVE TRANSFER; POTENT; MACAQUES; INFECTION; TRANSMISSION Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/27591