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PLoS One. 2019 Aug 8;14(8):e0219142. doi: 10.1371/journal.pone.0219142. eCollection 2019.

Safety, pharmacokinetics, and immunogenicity of the combination of the broadly neutralizing anti-HIV-1 antibodies 3BNC117 and 10-1074 in healthy adults: A randomized, phase 1 study.

Author information

1
Laboratory of Molecular Immunology, The Rockefeller University, New York, New York, United States of America.
2
Division of Infectious Diseases, Brigham and Women's Hospital, Boston, Massachusetts, United States of America.
3
Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire, United States of America.
4
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts, United States of America.
5
Vaccine and Infectious Disease Division and Statistical Center for HIV/AIDS Research and Prevention, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.
6
Duke Human Vaccine Institute, Duke University Medical Center, Durham, North Carolina, United States of America.
7
Departments of Surgery, Immunology, Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina, United States of America.
8
Howard Hughes Medical Institute, Chevy Chase, Maryland, United States of America.

Abstract

BACKGROUND:

Additional forms of pre-exposure prophylaxis are needed to prevent HIV-1 infection. 3BNC117 and 10-1074 are broadly neutralizing anti-HIV-1 antibodies that target non-overlapping epitopes on the HIV-1 envelope. We investigated the safety, tolerability, pharmacokinetics, and immunogenicity of the intravenous administration of the combination of 3BNC117 and 10-1074 in healthy adults.

METHODS:

This randomized, double-blind, placebo-controlled, single center, phase 1 study enrolled healthy adults aged 18-65 years to receive one infusion of 3BNC117 immediately followed by 10-1074 at 10 mg/kg, three infusions of 3BNC117 followed by 10-1074 at 3 mg/kg or 10 mg/kg every 8 weeks, or placebo infusions. The primary outcomes were safety and pharmacokinetics. This trial is registered with ClinicalTrials.gov, number NCT02824536.

FINDINGS:

Twenty-four participants were enrolled in a 3:1 ratio to receive the study products or placebo. The combination of 3BNC117 and 10-1074 was safe and generally well tolerated. There were no serious adverse events considered related to the infusions. The mean elimination half-lives of 3BNC117 and 10-1074 were 16.4 ± 4.6 days and 23.0 ± 5.4 days, respectively, similar to what was observed in previous studies in which each antibody was administered alone. Anti-drug antibody responses were rare and without evidence of related adverse events or impact on elimination kinetics.

INTERPRETATION:

Single and repeated doses of the combination of 3BNC117 and 10-1074 were well tolerated in healthy adults. These data support the further development of the combination of 3BNC117 and 10-1074 as a long-acting injectable form of pre-exposure prophylaxis for the prevention of HIV-1 infection.

Conflict of interest statement

I have read the journal’s policy and the authors of this manuscript have the following competing interests: There are patents on 3BNC117 (US Provisional Application No. 61/715,642) and 10-1074 (US Provisional Application No. 61/486,960) on which MCN is an inventor. The authors declare no further conflicts of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

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