Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants

被引：69

作者：

Klein, Florian ^{[1
]}

Nogueira, Lilian ^{[1
]}

Nishimura, Yoshiaki ^{[3
]}

Phad, Ganesh ^{[4
]}

West, Anthony P., Jr. ^{[5
]}

Halper-Stromberg, Ariel ^{[1
]}

Horwitz, Joshua A. ^{[1
]}

Gazumyan, Anna ^{[1
]}

Liu, Cassie ^{[1
]}

Eisenreich, Thomas R. ^{[1
]}

Lehmann, Clara ^{[7
]}

Faetkenheuer, Gerd ^{[7
]}

Williams, Constance ^{[8
]}

Shingai, Masashi ^{[3
]}

Martin, Malcolm A. ^{[3
]}

Bjorkman, Pamela J. ^{[5
,6
]}

Seaman, Michael S. ^{[9
]}

Zolla-Pazner, Susan ^{[8
,10
]}

Hedestam, Gunilla B. Karlsson ^{[4
]}

Nussenzweig, Michel C. ^{[1
,2
]}

机构：

[1] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA

[2] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA

[3] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA

[4] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17177 Stockholm, Sweden

[5] CALTECH, Div Biol, Pasadena, CA 91125 USA

[6] CALTECH, Howard Hughes Med Inst, Pasadena, CA 91125 USA

[7] Univ Hosp Cologne, Dept Internal Med 1, D-50924 Cologne, Germany

[8] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA

[9] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Ctr Virol & Vaccine Res, Boston, MA 02215 USA

[10] Vet Affairs Med Ctr, Res Serv, New York, NY 10010 USA

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2014年 / 211卷 / 12期

基金：

美国国家卫生研究院; 瑞典研究理事会;

关键词：

BROADLY NEUTRALIZING ANTIBODIES; SIMIAN IMMUNODEFICIENCY VIRUS; HUMORAL IMMUNE-RESPONSES; BINDING-SITE ANTIBODIES; V3; LOOP; ENVELOPE PROTEIN; RHESUS-MONKEYS; HUMANIZED MICE; TYPE-1; SF162; B-CELLS;

D O I：

10.1084/jem.20141050

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Antibody-mediated immunotherapy is effective in humanized mice when combinations of broadly neutralizing antibodies (bNAbs) are used that target nonoverlapping sites on the human immunodeficiency virus type 1 (HIV-1) envelope. In contrast, single bNAbs can control simian-human immunodeficiency virus (SHIV) infection in immune-competent macaques, suggesting that the host immune response might also contribute to the control of viremia. Here, we investigate how the autologous antibody response in intact hosts can contribute to the success of immunotherapy. We find that frequently arising antibodies that normally fail to control HIV-1 infection can synergize with passively administered bNAbs by preventing the emergence of bNAb viral escape variants.

引用

收藏

页码：2361 / 2372

页数：12

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