Universität zu Köln

Nishimura, Yoshiaki, Gautam, Rajeev, Chun, Tae-Wook ORCID: 0000-0001-5153-7340, Sadjadpour, Reza, Foulds, Kathryn E., Shingai, Masashi, Klein, Florian, Gazumyan, Anna, Golijanin, Jovana, Donaldson, Mitzi, Donau, Olivia K., Plishka, Ronald J., Buckler-White, Alicia, Seaman, Michael S., Lifson, Jeffrey D., Koup, Richard A. ., Fauci, Anthony S., Nussenzweig, Michel C. . and Martin, Malcolm A. (2017). Early antibody therapy can induce long-lasting immunity to SHIV. Nature, 543 (7646). S. 559 - 573. LONDON: NATURE PUBLISHING GROUP. ISSN 1476-4687

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Abstract

Highly potent and broadly neutralizing anti-HIV-1 antibodies (bNAbs) have been used to prevent and treat lentivirus infections in humanized mice, macaques, and humans(1-12). In immunotherapy experiments, administration of bNAbs to chronically infected animals transiently suppresses virus replication, which invariably returns to pre-treatment levels and results in progression to clinical disease. Here we show that early administration of bNAbs in a macaque simian/human immunodeficiency virus (SHIV) model is associated with very low levels of persistent viraemia, which leads to the establishment of T-cell immunity and resultant longterm infection control. Animals challenged with SHIVAD8-EO by mucosal or intravenous routes received a single 2-week course of two potent passively transferred bNAbs (3BNC117 and 10-1074 (refs 13, 14)). Viraemia remained undetectable for 56-177 days, depending on bNAb half-life in vivo. Moreover, in the 13 treated monkeys, plasma virus loads subsequently declined to undetectable levels in 6 controller macaques. Four additional animals maintained their counts of T cells carrying the CD4 antigen (CD4+) and very low levels of viraemia persisted for over 2 years. The frequency of cells carrying replication-competent virus was less than 1 per 106 circulating CD4(+) T cells in the six controller macaques. Infusion of a T-cell-depleting anti-CD8 beta monoclonal antibody to the controller animals led to a specific decline in levels of CD8(+) T cells and the rapid reappearance of plasma viraemia. In contrast, macaques treated for 15 weeks with combination anti-retroviral therapy, beginning on day 3 after infection, experienced sustained rebound plasma viraemia when treatment was interrupted. Our results show that passive immunotherapy during acute SHIV infection differs from combination anti-retroviral therapy in that it facilitates the emergence of potent CD8(+) T-cell immunity able to durably suppress virus replication.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Nishimura, Yoshiaki UNSPECIFIED UNSPECIFIED UNSPECIFIED Gautam, Rajeev UNSPECIFIED UNSPECIFIED UNSPECIFIED Chun, Tae-Wook UNSPECIFIED orcid.org/0000-0001-5153-7340 UNSPECIFIED Sadjadpour, Reza UNSPECIFIED UNSPECIFIED UNSPECIFIED Foulds, Kathryn E. UNSPECIFIED UNSPECIFIED UNSPECIFIED Shingai, Masashi UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Florian UNSPECIFIED UNSPECIFIED UNSPECIFIED Gazumyan, Anna UNSPECIFIED UNSPECIFIED UNSPECIFIED Golijanin, Jovana UNSPECIFIED UNSPECIFIED UNSPECIFIED Donaldson, Mitzi UNSPECIFIED UNSPECIFIED UNSPECIFIED Donau, Olivia K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Plishka, Ronald J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Buckler-White, Alicia UNSPECIFIED UNSPECIFIED UNSPECIFIED Seaman, Michael S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lifson, Jeffrey D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Koup, Richard A. . UNSPECIFIED UNSPECIFIED UNSPECIFIED Fauci, Anthony S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nussenzweig, Michel C. . UNSPECIFIED UNSPECIFIED UNSPECIFIED Martin, Malcolm A. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-236367
DOI:	10.1038/nature21435
Journal or Publication Title:	Nature
Volume:	543
Number:	7646
Page Range:	S. 559 - 573
Date:	2017
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	LONDON
ISSN:	1476-4687
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language BROADLY NEUTRALIZING ANTIBODIES; SIMIAN/HUMAN IMMUNODEFICIENCY VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; PRIMARY HIV-1 INFECTION; CD4(+) T-CELLS; MONOCLONAL-ANTIBODIES; HUMANIZED MICE; RHESUS-MONKEYS; IN-VIVO; MACAQUES Multiple languages Multidisciplinary Sciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/23636