Glycans Function as Anchors for Antibodies and Help Drive HIV Broadly Neutralizing Antibody Development

被引：38

作者：

Andrabi, Raiees ^{[1
,2
,3
]}

Su, Ching-Yao ^{[1
,2
,3
]}

Liang, Chi-Hui ^{[1
,2
,3
]}

Shivatare, Sachin S. ^{[4
]}

Briney, Bryan ^{[1
,2
,3
]}

Voss, James E. ^{[1
,2
,3
]}

Nawazi, Salar Khan ^{[1
,2
]}

Wu, Chung-Yi ^{[4
]}

Wong, Chi-Huey ^{[4
]}

Burton, Dennis R. ^{[1
,2
,3
,5
]}

机构：

[1] Scripps Res Inst, Dept Immunol & Microbiol, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Neutralizing Antibody Ctr, Int AIDS Vaccine Initiat, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Ctr HIV AIDS Vaccine Immunol & Immunogen Discover, La Jolla, CA 92037 USA

[4] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan

[5] Ragon Inst Massachusetts Gen Hosp Massachusetts I, Cambridge, MA 02114 USA

来源：

IMMUNITY | 2017年 / 47卷 / 03期

关键词：

RECOGNITION; MATURATION; LINEAGE; EPITOPE; REVEAL; IMMUNIZATION; COEVOLUTION; PRECURSORS; BINDING; DESIGN;

D O I：

10.1016/j.immuni.2017.08.006

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Apex broadly neutralizing HIV antibodies (bnAbs) recognize glycans and protein surface close to the 3-fold axis of the envelope (Env) trimer and are among the most potent and broad Abs described. The evolution of apex bnAbs from one donor (CAP256) has been studied in detail and many Abs at different stages of maturation have been described. Using diverse engineering tools, we investigated the involvement of glycan recognition in the development of the CAP256. VRC26 Ab lineage. We found that sialic acid-bearing glycans were recognized by germline-encoded and somatically mutated residues on the Ab heavy chain. This recognition provided an "anchor'' for the Abs as the core protein epitope varies, prevented complete neutralization escape, and eventually led to broadening of the response. These findings illustrate how glycan-specific maturation enables a human Ab to cope with pathogen escape mechanisms and will aid in optimization of immunization strategies to induce V2 apex bnAb responses.

引用

页码：524 / +

页数：17

共 52 条

[1] Synthetic glycopeptides reveal the glycan specificity of HIV-neutralizing antibodies [J].

Amin, Mohammed N. ;

McLellan, Jason S. ;

Huang, Wei ;

Orwenyo, Jared ;

Burton, Dennis R. ;

Koff, Wayne C. ;

Kwong, Peter D. ;

Wang, Lai-Xi .

NATURE CHEMICAL BIOLOGY, 2013, 9 (08) :521-526

[2] Composition and Antigenic Effects of Individual Glycan Sites of a Trimeric HIV-1 Envelope Glycoprotein [J].

Behrens, Anna-Janina ;

Vasiljevic, Snezana ;

Pritchard, Laura K. ;

Harvey, David J. ;

Andev, Rajinder S. ;

Krumm, Stefanie A. ;

Struwe, Weston B. ;

Cupo, Albert ;

Kumar, Abhinav ;

Zitzmann, Nicole ;

Seabright, Gemma E. ;

Kramer, Holger B. ;

Spencer, Daniel I. R. ;

Royle, Louise ;

Lee, Jeong Hyun ;

Klasse, Per J. ;

Burton, Dennis R. ;

Wilson, Ian A. ;

Ward, Andrew B. ;

Sanders, Rogier W. ;

Moore, John P. ;

Doores, Katie J. ;

Crispin, Max .

CELL REPORTS, 2016, 14 (11) :2695-2706

[3] Viral variants that initiate and drive maturation of V1V2-directed HIV-1 broadly neutralizing antibodies [J].

Bhiman, Jinal N. ;

Anthony, Colin ;

Doria-Rose, Nicole A. ;

Karimanzira, Owen ;

Schramm, Chaim A. ;

Khoza, Thandeka ;

Kitchin, Dale ;

Botha, Gordon ;

Gorman, Jason ;

Garrett, Nigel J. ;

Karim, Salim S. Abdool ;

Shapiro, Lawrence ;

Williamson, Carolyn ;

Kwong, Peter D. ;

Mascola, John R. ;

Morris, Lynn ;

Moore, Penny L. .

NATURE MEDICINE, 2015, 21 (11) :1332-1336

[4] Antibody-virus co-evolution in HIV infection: paths for HIV vaccine development [J].

Bonsignori, Mattia ;

Liao, Hua-Xin ;

Gao, Feng ;

Williams, Wilton B. ;

Alam, S. Munir ;

Montefiori, David C. ;

Haynes, Barton F. .

IMMUNOLOGICAL REVIEWS, 2017, 275 (01) :145-160

[5] Analysis of a Clonal Lineage of HIV-1 Envelope V2/V3 Conformational Epitope-Specific Broadly Neutralizing Antibodies and Their Inferred Unmutated Common Ancestors [J].

Bonsignori, Mattia ;

Hwang, Kwan-Ki ;

Chen, Xi ;

Tsao, Chun-Yen ;

Morris, Lynn ;

Gray, Elin ;

Marshall, Dawn J. ;

Crump, John A. ;

Kapiga, Saidi H. ;

Sam, Noel E. ;

Sinangil, Faruk ;

Pancera, Marie ;

Yang Yongping ;

Zhang, Baoshan ;

Zhu, Jiang ;

Kwong, Peter D. ;

O'Dell, Sijy ;

Mascola, John R. ;

Wu, Lan ;

Nabel, Gary J. ;

Phogat, Sanjay ;

Seaman, Michael S. ;

Whitesides, John F. ;

Moody, M. Anthony ;

Kelsoe, Garnett ;

Yang, Xinzhen ;

Sodroski, Joseph ;

Shaw, George M. ;

Montefiori, David C. ;

Kepler, Thomas B. ;

Tomaras, Georgia D. ;

Alam, S. Munir ;

Liao, Hua-Xin ;

Haynes, Barton F. .

JOURNAL OF VIROLOGY, 2011, 85 (19) :9998-10009

[6] Tailored Immunogens Direct Affinity Maturation toward HIV Neutralizing Antibodies [J].

Briney, Bryan ;

Sok, Devin ;

Jardine, Joseph G. ;

Kulp, Daniel W. ;

Skog, Patrick ;

Menis, Sergey ;

Jacak, Ronald ;

Kalyuzhniy, Oleksandr ;

de Val, Natalia ;

Sesterhenn, Fabian ;

Le, Khoa M. ;

Ramos, Alejandra ;

Jones, Meaghan ;

Saye-Francisco, Karen L. ;

Blane, Tanya R. ;

Spencer, Skye ;

Georgeson, Erik ;

Hu, Xiaozhen ;

Ozorowski, Gabriel ;

Adachi, Yumiko ;

Kubitz, Michael ;

Sarkar, Anita ;

Wilson, Ian A. ;

Ward, Andrew B. ;

Nemazee, David ;

Burton, Dennis R. ;

Schief, William R. .

CELL, 2016, 166 (06) :1459-+

[7] Clonify: unseeded antibody lineage assignment from next-generation sequencing data [J].

Briney, Bryan ;

Le, Khoa ;

Zhu, Jiang ;

Burton, Dennis R. .

SCIENTIFIC REPORTS, 2016, 6

[8] Antibodies, viruses and vaccines [J].

Burton, DR .

NATURE REVIEWS IMMUNOLOGY, 2002, 2 (09) :706-713

[9] Global site-specific N-glycosylation analysis of HIV envelope glycoprotein [J].

Cao, Liwei ;

Diedrich, Jolene K. ;

Kulp, Daniel W. ;

Pauthner, Matthias ;

He, Lin ;

Park, Sung-Kyu Robin ;

Sok, Devin ;

Su, Ching Yao ;

Delahunty, Claire M. ;

Menis, Sergey ;

Andrabi, Raiees ;

Guenaga, Javier ;

Georgeson, Erik ;

Kubitz, Michael ;

Adachi, Yumiko ;

Burton, Dennis R. ;

Schief, William R. ;

Yates, John R., III ;

Paulson, James C. .

NATURE COMMUNICATIONS, 2017, 8

[10] Therapeutic antibodies, vaccines and antibodyomes [J].

Dimitrov, Dimiter S. .

MABS, 2010, 2 (03) :347-356

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