Antibody 10-1074 suppresses viremia in HIV-1-infected individuals

被引：373

作者：

Caskey, Marina ^{[1
]}

Schoofs, Till ^{[1
]}

Gruell, Henning ^{[2
,3
,4
]}

Settler, Allison ^{[1
]}

Karagounis, Theodora ^{[1
]}

Kreider, Edward F. ^{[5
,6
]}

Murrell, Ben ^{[7
]}

Pfeifer, Nico ^{[8
]}

Nogueira, Lilian ^{[1
]}

Oliveira, Thiago Y. ^{[1
]}

Learn, Gerald H. ^{[5
,6
]}

Cohen, Yehuda Z. ^{[1
]}

Lehmann, Clara ^{[3
,4
]}

Gillor, Daniel ^{[3
]}

Shimeliovich, Irma ^{[1
]}

Unson-O'Brien, Cecilia ^{[1
]}

Weiland, Daniela ^{[2
,3
,4
]}

Robles, Alexander ^{[9
]}

Kuemmerle, Tim ^{[3
]}

Wyen, Christoph ^{[3
]}

Levin, Rebeka ^{[1
]}

Witmer-Pack, Maggi ^{[1
]}

Eren, Kemal ^{[10
,11
]}

Ignacio, Caroline ^{[7
]}

Kiss, Szilard ^{[12
]}

West, Anthony P., Jr. ^{[13
]}

Mouquet, Hugo ^{[14
]}

Zingman, Barry S. ^{[15
,16
]}

Gulick, Roy M. ^{[17
]}

Keler, Tibor ^{[18
]}

Bjorkman, Pamela J. ^{[13
]}

Seaman, Michael S. ^{[9
]}

Hahn, Beatrice H. ^{[5
,6
]}

Faetkenheuer, Gerd ^{[3
,4
]}

Schlesinger, Sarah J. ^{[1
]}

Nussenzweig, Michel C. ^{[1
,19
]}

Klein, Florian ^{[2
,3
,4
]}

机构：

[1] Rockefeller Univ, Lab Mol Immunol, 1230 York Ave, New York, NY 10021 USA

[2] Univ Cologne, Expt Immunol Lab, Ctr Mol Med Cologne, Cologne, Germany

[3] Univ Hosp Cologne, Dept Internal Med 1, Cologne, Germany

[4] German Ctr Infect Res, Partner Site Bonn Cologne, Cologne, Germany

[5] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA

[6] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA

[7] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA

[8] Max Planck Inst Informat, Dept Computat Biol & Appl Algorithm, Saarbrucken, Germany

[9] Harvard Med Sch, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA USA

[10] Univ Calif San Diego, Dept Biomed Informat, San Diego, CA USA

[11] Univ Calif San Diego, Bioinformat & Syst Biol, San Diego, CA 92103 USA

[12] Cornell Univ, Weill Carnell Med Coll, Dept Ophthalmol, New York, NY 10021 USA

[13] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA

[14] Inst Pasteur, Dept Immunol, Lab Humoral Response Pathogens, Paris, France

[15] Montefiore Med Ctr, Albert Einstein Coll Med, Div Infect Dis, Bronx, NY 10467 USA

[16] Einstein Rockefeller CUNY Ctr AIDS Res, Bronx, NY USA

[17] Weill Cornell Med, Div Infect Dis, New York, NY USA

[18] Celldex Therapeut, Hampton, VA USA

[19] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA

来源：

NATURE MEDICINE | 2017年 / 23卷 / 02期

基金：

欧洲研究理事会; 美国国家卫生研究院;

关键词：

BROADLY NEUTRALIZING ANTIBODIES; HUMAN MONOCLONAL-ANTIBODIES; HIV-1; VACCINE; GLYCAN RECOGNITION; PASSIVE TRANSFER; IN-VIVO; POTENT; VRC01; THERAPY; PHARMACOKINETICS;

D O I：

10.1038/nm.4268

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Monoclonal antibody 10-1074 targets the V3 glycan supersite on the HIV-1 envelope (Env) protein. It is among the most potent anti-HIV-1 neutralizing antibodies isolated so far. Here we report on its safety and activity in 33 individuals who received a single intravenous infusion of the antibody. 10-1074 was well tolerated and had a half-life of 24.0 d in participants without HIV-1 infection and 12.8 d in individuals with HIV-1 infection. Thirteen individuals with viremia received the highest dose of 30 mg/kg 10-1074. Eleven of these participants were 10-1074-sensitive and showed a rapid decline in viremia by a mean of 1.52 logic copies/ml. Virologic analysis revealed the emergence of multiple independent 10-1074-resistant viruses in the first weeks after infusion. Emerging escape variants were generally resistant to the related V3-specific antibody PGT121, but remained sensitive to antibodies targeting nonoverlapping epitopes, such as the anti-CD4-binding-site antibodies 3BNC117 and VRC01. The results demonstrate the safety and activity of 10-1074 in humans and support the idea that antibodies targeting the V3 glycan supersite might be useful for the treatment and prevention of HIV-1 infection.

引用

页码：185 / 191

页数：7

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