Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Analysis of HIV-1 latent reservoir and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117

View ORCID ProfileYehuda Z. Cohen, View ORCID ProfileJulio C. C. Lorenzi, Lisa Krassnig, View ORCID ProfileJohn P. Barton, Leah Burke, Joy Pai, Ching-Lan Lu, Pilar Mendoza, View ORCID ProfileThiago Y. Oliveira, Christopher Sleckman, Katrina Millard, Allison L. Butler, Juan P. Dizon, Shiraz A. Belblidia, Maggi Witmer-Pack, Irina Shimeliovich, Roy M. Gulick, View ORCID ProfileMichael S. Seaman, Mila Jankovic, View ORCID ProfileMarina Caskey, View ORCID ProfileMichel C. Nussenzweig
doi: https://doi.org/10.1101/324509
Yehuda Z. Cohen
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yehuda Z. Cohen
Julio C. C. Lorenzi
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Julio C. C. Lorenzi
Lisa Krassnig
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John P. Barton
2Department of Physics and Astronomy, University of California, Riverside, CA 92521, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for John P. Barton
Leah Burke
3Division of Infectious Diseases, Weill Cornell Medicine, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Joy Pai
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ching-Lan Lu
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pilar Mendoza
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Thiago Y. Oliveira
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Thiago Y. Oliveira
Christopher Sleckman
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katrina Millard
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Allison L. Butler
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juan P. Dizon
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shiraz A. Belblidia
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Maggi Witmer-Pack
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Irina Shimeliovich
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Roy M. Gulick
3Division of Infectious Diseases, Weill Cornell Medicine, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael S. Seaman
4Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Michael S. Seaman
Mila Jankovic
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marina Caskey
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Marina Caskey
  • For correspondence: nussen@rockefeller.edu mcaskey@rockefeller.edu
Michel C. Nussenzweig
1Laboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065, USA
5Howard Hughes Medical Institute
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Michel C. Nussenzweig
  • For correspondence: nussen@rockefeller.edu mcaskey@rockefeller.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

A clinical trial was performed to evaluate 3BNC117, a potent anti_HIV_1 antibody, in infected individuals during suppressive antiretroviral therapy (ART) and subsequent analytical treatment interruption (ATI). The circulating reservoir was evaluated by quantitative and qualitative outgrowth assay (Q2VOA) at entry and after 6 months, prior to ATI. Although there were no significant quantitative changes in the size of the reservoir, the composition of circulating reservoir clones varied over the 6_month period before treatment interruption in a manner that did not correlate with antibody sensitivity. The neutralization profile obtained from the reservoir by Q2VOA was predictive of time to rebound after ATI, and thus of antibody efficacy. Although 3BNC117 binding site amino acid variants found in rebound viruses pre_existed in the latent reservoir, only 3 of 217 rebound viruses were identical to 868 latent viruses. Instead many of the rebound viruses appeared to be recombinants, even in individuals with resistant reservoir viruses. By incorporating the possibility of recombination, 63% of the rebound viruses could have derived from the observed latent reservoir. In conclusion, viruses emerging during ATI in individuals treated with 3BNC117 are not the dominant species found in the circulating reservoir, but instead appear to represent recombinants.

Summary In the setting of a clinical trial evaluating the anti_HIV_1 antibody 3BNC117, Cohen et al. demonstrate that rebound viruses that emerge following interruption of antiretroviral therapy are distinct from circulating latent viruses. However, rebound viruses often appear to be recombinants between isolated latent viruses.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted May 25, 2018.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Analysis of HIV-1 latent reservoir and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Analysis of HIV-1 latent reservoir and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117
Yehuda Z. Cohen, Julio C. C. Lorenzi, Lisa Krassnig, John P. Barton, Leah Burke, Joy Pai, Ching-Lan Lu, Pilar Mendoza, Thiago Y. Oliveira, Christopher Sleckman, Katrina Millard, Allison L. Butler, Juan P. Dizon, Shiraz A. Belblidia, Maggi Witmer-Pack, Irina Shimeliovich, Roy M. Gulick, Michael S. Seaman, Mila Jankovic, Marina Caskey, Michel C. Nussenzweig
bioRxiv 324509; doi: https://doi.org/10.1101/324509
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Analysis of HIV-1 latent reservoir and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117
Yehuda Z. Cohen, Julio C. C. Lorenzi, Lisa Krassnig, John P. Barton, Leah Burke, Joy Pai, Ching-Lan Lu, Pilar Mendoza, Thiago Y. Oliveira, Christopher Sleckman, Katrina Millard, Allison L. Butler, Juan P. Dizon, Shiraz A. Belblidia, Maggi Witmer-Pack, Irina Shimeliovich, Roy M. Gulick, Michael S. Seaman, Mila Jankovic, Marina Caskey, Michel C. Nussenzweig
bioRxiv 324509; doi: https://doi.org/10.1101/324509

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Clinical Trials
Subject Areas
All Articles
  • Animal Behavior and Cognition (4095)
  • Biochemistry (8793)
  • Bioengineering (6495)
  • Bioinformatics (23406)
  • Biophysics (11769)
  • Cancer Biology (9173)
  • Cell Biology (13304)
  • Clinical Trials (138)
  • Developmental Biology (7426)
  • Ecology (11392)
  • Epidemiology (2066)
  • Evolutionary Biology (15127)
  • Genetics (10419)
  • Genomics (14029)
  • Immunology (9154)
  • Microbiology (22132)
  • Molecular Biology (8797)
  • Neuroscience (47470)
  • Paleontology (350)
  • Pathology (1423)
  • Pharmacology and Toxicology (2486)
  • Physiology (3712)
  • Plant Biology (8073)
  • Scientific Communication and Education (1434)
  • Synthetic Biology (2217)
  • Systems Biology (6023)
  • Zoology (1251)