Universität zu Köln

Lee, Wen Shi ORCID: 0000-0001-7285-4054, Kristensen, Anne B., Rasmussen, Thomas A., Tolstrup, Martin ORCID: 0000-0001-7020-5173, Ostergaard, Lars ORCID: 0000-0002-7619-605X, Sogaard, Ole S., Wines, Bruce D., Hogarth, P. Mark, Reynaldi, Arnold ORCID: 0000-0002-5529-5542, Davenport, Miles P., Emery, Sean ORCID: 0000-0001-6072-8309, Amin, Janaki ORCID: 0000-0003-2161-9366, Cooper, David A., Kan, Virginia L., Fox, Julie, Gruell, Henning, Parsons, Matthew S. and Kent, Stephen J. (2017). Anti-HIV-1 ADCC Antibodies following Latency Reversal and Treatment Interruption. J. Virol., 91 (15). WASHINGTON: AMER SOC MICROBIOLOGY. ISSN 1098-5514

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Abstract

There is growing interest in utilizing antibody-dependent cellular cytotoxicity (ADCC) to eliminate infected cells following reactivation from HIV-1 latency. A potential barrier is that HIV-1-specific ADCC antibodies decline in patients on long-term antiretroviral therapy (ART) and may not be sufficient to eliminate reactivated latently infected cells. It is not known whether reactivation from latency with latency-reversing agents (LRAs) could provide sufficient antigenic stimulus to boost HIV-1-specific ADCC. We found that treatment with the LRA panobinostat or a short analytical treatment interruption (ATI), 21 to 59 days, was not sufficient to stimulate an increase in ADCC-competent antibodies, despite viral rebound in all subjects who underwent the short ATI. In contrast, a longer ATI, 2 to 12 months, among subjects enrolled in the Strategies for Management of Antiretroviral Therapy (SMART) trial robustly boosted HIV-1 gp120-specific Fc receptor-binding antibodies and ADCC against HIV-1-infected cells in vitro. These results show that there is a lag between viral recrudescence and the boosting of ADCC antibodies, which has implications for strategies toward eliminating latently infected cells. IMPORTANCE The shock and kill HIV-1 cure strategy aims to reactivate HIV-1 expression in latently infected cells and subsequently eliminate the reactivated cells through immune-mediated killing. Several latency reversing agents (LRAs) have been examined in vivo, but LRAs alone have not been able to achieve HIV-1 remission and prevent viral rebound following analytical treatment interruption (ATI). In this study, we examined whether LRA treatment or ATI can provide sufficient antigenic stimulus to boost HIV-1-specific functional antibodies that can eliminate HIV-1-infected cells. Our study has implications for the antigenic stimulus required for antilatency strategies and/or therapeutic vaccines to boost functional antibodies and assist in eliminating the latent reservoir.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lee, Wen Shi UNSPECIFIED orcid.org/0000-0001-7285-4054 UNSPECIFIED Kristensen, Anne B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Rasmussen, Thomas A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tolstrup, Martin UNSPECIFIED orcid.org/0000-0001-7020-5173 UNSPECIFIED Ostergaard, Lars UNSPECIFIED orcid.org/0000-0002-7619-605X UNSPECIFIED Sogaard, Ole S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wines, Bruce D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hogarth, P. Mark UNSPECIFIED UNSPECIFIED UNSPECIFIED Reynaldi, Arnold UNSPECIFIED orcid.org/0000-0002-5529-5542 UNSPECIFIED Davenport, Miles P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Emery, Sean UNSPECIFIED orcid.org/0000-0001-6072-8309 UNSPECIFIED Amin, Janaki UNSPECIFIED orcid.org/0000-0003-2161-9366 UNSPECIFIED Cooper, David A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kan, Virginia L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fox, Julie UNSPECIFIED UNSPECIFIED UNSPECIFIED Gruell, Henning UNSPECIFIED UNSPECIFIED UNSPECIFIED Parsons, Matthew S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kent, Stephen J. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-224179
DOI:	10.1128/JVI.00603-17
Journal or Publication Title:	J. Virol.
Volume:	91
Number:	15
Date:	2017
Publisher:	AMER SOC MICROBIOLOGY
Place of Publication:	WASHINGTON
ISSN:	1098-5514
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DEPENDENT CELLULAR CYTOTOXICITY; BROADLY NEUTRALIZING ANTIBODIES; CD4(+) T-CELLS; HIV-1-INFECTED CELLS; THERAPEUTIC VACCINATION; ANTIRETROVIRAL THERAPY; EFFECTOR FUNCTIONS; HIV-1; ACTIVATION; EXPRESSION Multiple languages Virology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/22417