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

共 50 条

[31] VISCERAL LEISHMANIASIS IN HIV-1-INFECTED INDIVIDUALS - A COMMON OPPORTUNISTIC INFECTION IN SPAIN
MEDRANO, FJ
HERNANDEZQUERO, J
JIMENEZ, E
PINEDA, JA
RIVERO, A
SANCHEZQUIJANO, A
VELEZ, ID
VICIANA, P
CASTILLO, R
REYES, MJ
CARVAJAL, F
LEAL, M
LISSEN, E
AIDS, 1992, 6 (12) : 1499 - 1503
[32] Elimination of latently HIV-1-infected cells by lymphoblasts armed with bifunctional antibody
Yin, SP
Okada, N
Okada, H
MICROBIOLOGY AND IMMUNOLOGY, 2001, 45 (01) : 101 - 108
[33] IL-10 induces activated phenotypes of monocytes observed in virally-suppressed HIV-1-infected individuals
Takahashi, Naofumi
Eltalkhawy, Youssef M.
Nasu, Kanako
Abdelnaser, Randa A.
Monde, Kazuaki
Habash, Sara A.
Nasser, Hesham
Hiyoshi, Masateru
Ishimoto, Takatsugu
Suzu, Shinya
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2024, 729
[34] 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
Cohen, Yehuda Z.
Butler, Allison L.
Millard, Katrina
Witmer-Pack, Maggi
Levin, Rebeka
Unson-O'Brien, Cecilia
Patel, Roshni
Shimeliovich, Irina
Lorenzi, Julio C. C.
Horowitz, Jill
Walsh, Stephen R.
Lin, Shu
Weiner, Joshua A.
Tse, Anna
Sato, Alicia
Bennett, Chelsey
Mayer, Bryan
Seaton, Kelly E.
Yates, Nicole L.
Baden, Lindsey R.
deCamp, Allan C.
Ackerman, Margaret E.
Seaman, Michael S.
Tomaras, Georgia D.
Nussenzweig, Michel C.
Caskey, Marina
PLOS ONE, 2019, 14 (08):
[35] Uncovering HIV-1-infected cells
Veillette, Maxime
Richard, Jonathan
Finzi, Andres
ONCOTARGET, 2015, 6 (26) : 21791 - 21792
[36] Semen of HIV-1-Infected Individuals: Local Shedding of Herpesviruses and Reprogrammed Cytokine Network
Lisco, Andrea
Munawwar, Arshi
Introini, Andrea
Vanpouille, Christophe
Saba, Elisa
Feng, Xingmin
Grivel, Jean-Charles
Singh, Sarman
Margolis, Leonid
JOURNAL OF INFECTIOUS DISEASES, 2012, 205 (01) : 97 - 105
[37] Immune perturbations in HIV-1-infected individuals who make broadly neutralizing antibodies
Moody, M. Anthony
Pedroza-Pacheco, Isabela
Vandergrift, Nathan A.
Chui, Cecilia
Lloyd, Krissey E.
Parks, Robert
Soderberg, Kelly A.
Ogbe, Ane T.
Cohen, Myron S.
Liao, Hua-Xin
Gao, Feng
McMichael, Andrew J.
Montefiori, David C.
Verkoczy, Laurent
Kelsoe, Garnett
Huang, Jinghe
Shea, Patrick R.
Connors, Mark
Borrow, Persephone
Haynes, Barton F.
SCIENCE IMMUNOLOGY, 2016, 1 (01)
[38] Antibody-Dependent Cellular Cytotoxicity-Competent Antibodies against HIV-1-Infected Cells in Plasma from HIV-Infected Subjects
Dupuy, Franck P.
Kant, Sanket
Barbe, Alexandre
Routy, Jean-Pierre
Bruneau, Julie
Lebouche, Bertrand
Tremblay, Cecile
Pazgier, Marzena
Finzi, Andres
Bernard, Nicole F.
MBIO, 2019, 10 (06):
[39] Proliferation, But Not Interleukin 2 Production, of Gag-Specific CD8+ T Cells Is Associated With Low HIV Viremia and High CD4 Counts in HIV-1-infected Chinese Individuals
Li, Haiying
Chen, Xinyue
Jin, Xia
Liu, Zhiying
Huang, Xiaojie
Cao, Zhenhuan
Guo, Caiping
Dong, Tao
Wu, Hao
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 2009, 52 (01) : 1 - 8
[40] Increased levels of galactose-deficient IgG in sera of HIV-1-infected individuals
Moore, JS
Wu, XL
Kulhavy, R
Tomana, M
Novak, J
Moldoveanu, Z
Brown, R
Goepfert, PA
Mestecky, J
AIDS, 2005, 19 (04) : 381 - 389

← 1 2 3 4 5 →