Host Anti-antibody Responses Following Adeno-associated Virus-mediated Delivery of Antibodies Against HIV and SIV in Rhesus Monkeys

Martinez-Navio JM, Fuchs S, Pedreno-Lopez S, Rakasz EG, Gao G, Desrosiers RC (2016)

Publication Type: Journal article

Publication year: 2016

Journal

Molecular Therapy Cell Press

Book Volume: 24

Pages Range: 76-86

Journal Issue: 1

DOI: 10.1038/mt.2015.191

Abstract

Long-term delivery of antibodies against the human immunodeficiency virus (HIV) using adeno-associated virus (AAV) vectors is a promising approach for the prevention or treatment of HIV infection. However, host antibody responses to the delivered antibody are a serious concern that could significantly limit the applicability of this approach. Here, we describe the dynamics and characteristics of the anti-antibody responses in monkeys that received either rhesus anti-simian immunodeficiency virus (SIV) antibodies (4L6 or 5L7) in prevention trials or a combination of rhesusized human anti-HIV antibodies (1NC9/8ANC195/3BNC117 or 10-1074/10E8/3BNC117) in therapy trials, all employing AAV1 delivery of IgG1. Eight out of eight monkeys that received the anti-HIV antibodies made persisting antibody responses to all three antibodies in the mix. Six out of six uninfected monkeys that received the anti-SIV antibody 4L6 and three out of six of those receiving anti-SIV antibody 5L7 also generated anti-antibodies. Both heavy and light chains were targeted, predominantly or exclusively to variable regions, and reactivity to complementarity-determining region (CDR)-H3 peptide could be demonstrated. There was a highly significant correlation of the magnitude of anti-antibody responses with the degree of sequence divergence of the delivered antibody from germline. Our results suggest the need for effective strategies to counteract the problem of antibody responses to AAV-delivered antibodies.

Authors with CRIS profile

Sebastian Fuchs Lehrstuhl für Klinische und Molekulare Virologie

Involved external institutions

University of Miami US United States (USA) (US) University of Massachusetts Amherst (UMass) US United States (USA) (US) University of Wisconsin - Madison US United States (USA) (US)

How to cite

APA:

Martinez-Navio, J.M., Fuchs, S., Pedreno-Lopez, S., Rakasz, E.G., Gao, G., & Desrosiers, R.C. (2016). Host Anti-antibody Responses Following Adeno-associated Virus-mediated Delivery of Antibodies Against HIV and SIV in Rhesus Monkeys. Molecular Therapy, 24(1), 76-86. https://doi.org/10.1038/mt.2015.191

MLA:

Martinez-Navio, Jose M., et al. "Host Anti-antibody Responses Following Adeno-associated Virus-mediated Delivery of Antibodies Against HIV and SIV in Rhesus Monkeys." Molecular Therapy 24.1 (2016): 76-86.

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