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

[11] Variable Loop Glycan Dependency of the Broad and Potent HIV-1-Neutralizing Antibodies PG9 and PG16 [J].

Doores, Katie J. ;

Burton, Dennis R. .

JOURNAL OF VIROLOGY, 2010, 84 (20) :10510-10521

[12] New Member of the V1V2-Directed CAP256-VRC26 Lineage That Shows Increased Breadth and Exceptional Potency [J].

Doria-Rose, Nicole A. ;

Bhiman, Jinal N. ;

Roark, Ryan S. ;

Schramm, Chaim A. ;

Gorman, Jason ;

Chuang, Gwo-Yu ;

Pancera, Marie ;

Cale, Evan M. ;

Ernandes, Michael J. ;

Louder, Mark K. ;

Asokan, Mangaiarkarasi ;

Bailer, Robert T. ;

Druz, Aliaksandr ;

Fraschilla, Isabella R. ;

Garrett, Nigel J. ;

Jarosinski, Marissa ;

Lynch, Rebecca M. ;

McKee, Krisha ;

O'Dell, Sijy ;

Pegu, Amarendra ;

Schmidt, Stephen D. ;

Staupe, Ryan P. ;

Sutton, Matthew S. ;

Wang, Keyun ;

Wibmer, Constantinos Kurt ;

Haynes, Barton F. ;

Abdool-Karim, Salim ;

Shapiro, Lawrence ;

Kwong, Peter D. ;

Moore, Penny L. ;

Morris, Lynn ;

Mascola, John R. .

JOURNAL OF VIROLOGY, 2016, 90 (01) :76-91

[13] Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies [J].

Doria-Rose, Nicole A. ;

Schramm, Chaim A. ;

Gorman, Jason ;

Moore, Penny L. ;

Bhiman, Jinal N. ;

DeKosky, Brandon J. ;

Ernandes, Michael J. ;

Georgiev, Ivelin S. ;

Kim, Helen J. ;

Pancera, Marie ;

Staupe, Ryan P. ;

Altae-Tran, Han R. ;

Bailer, Robert T. ;

Crooks, Ema T. ;

Cupo, Albert ;

Druz, Aliaksandr ;

Garrett, Nigel J. ;

Hoi, Kam H. ;

Kong, Rui ;

Louder, Mark K. ;

Longo, Nancy S. ;

McKee, Krisha ;

Nonyane, Molati ;

O'Dell, Sijy ;

Roark, Ryan S. ;

Rudicell, Rebecca S. ;

Schmidt, Stephen D. ;

Sheward, Daniel J. ;

Soto, Cinque ;

Wibmer, Constantinos Kurt ;

Yang, Yongping ;

Zhang, Zhenhai ;

Mullikin, James C. ;

Binley, James M. ;

Sanders, Rogier W. ;

Wilson, Ian A. ;

Moore, John P. ;

Ward, Andrew B. ;

Georgiou, George ;

Williamson, Carolyn ;

Karim, Salim S. Abdool ;

Morris, Lynn ;

Kwong, Peter D. ;

Shapiro, Lawrence ;

Mascola, John R. .

NATURE, 2014, 509 (7498) :55-+

[14] Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice [J].

Dosenovic, Pia ;

von Boehmer, Lotta ;

Escolano, Amelia ;

Jardine, Joseph ;

Freund, Natalia T. ;

Gitlin, Alexander D. ;

McGuire, Andrew T. ;

Kulp, Daniel W. ;

Oliveira, Thiago ;

Scharf, Louise ;

Pietzsch, John ;

Gray, Matthew D. ;

Cupo, Albert ;

van Gils, Marit J. ;

Yao, Kai-Hui ;

Liu, Cassie ;

Gazumyan, Anna ;

Seaman, Michael S. ;

Bjoerkman, Pamela J. ;

Sanders, Rogier W. ;

Moore, John P. ;

Stamatatos, Leonidas ;

Schief, William R. ;

Nussenzweig, Michel C. .

CELL, 2015, 161 (07) :1505-1515

[15] MUSCLE: multiple sequence alignment with high accuracy and high throughput [J].

Edgar, RC .

NUCLEIC ACIDS RESEARCH, 2004, 32 (05) :1792-1797

[16] Sequential Immunization Elicits Broadly Neutralizing Anti-HIV-1 Antibodies in Ig Knockin Mice [J].

Escolano, Amelia ;

Steichen, Jon M. ;

Dosenovic, Pia ;

Kulp, Daniel W. ;

Golijanin, Jovana ;

Sok, Devin ;

Freund, Natalia T. ;

Gitlin, Alexander D. ;

Oliveira, Thiago ;

Araki, Tatsuya ;

Lowe, Sarina ;

Chen, Spencer T. ;

Heinemann, Jennifer ;

Yao, Kai-Hui ;

Georgeson, Erik ;

Saye-Francisco, Karen L. ;

Gazumyan, Anna ;

Adachi, Yumiko ;

Kubitz, Michael ;

Burton, Dennis R. ;

Schief, William R. ;

Nussenzweig, Michel C. .

CELL, 2016, 166 (06) :1445-+

[17] Broadly Neutralizing HIV Antibodies Define a Glycan-Dependent Epitope on the Prefusion Conformation of gp41 on Cleaved Envelope Trimers [J].

Falkowska, Emilia ;

Le, Khoa M. ;

Ramos, Alejandra ;

Doores, Katie J. ;

Lee, Jeong Hyun ;

Blattner, Claudia ;

Ramirez, Alejandro ;

Derking, Ronald ;

van Gils, Marit J. ;

Liang, Chi-Hui ;

Mcbride, Ryan ;

von Bredow, Benjamin ;

Shivatare, Sachin S. ;

Wu, Chung-Yi ;

Chan-Hui, Po-Ying ;

Liu, Yan ;

Feizi, Ten ;

Zwick, Michael B. ;

Koff, Wayne C. ;

Seaman, Michael S. ;

Swiderek, Kristine ;

Moore, John P. ;

Evans, David ;

Paulson, James C. ;

Wong, Chi-Huey ;

Ward, Andrew B. ;

Wilson, Ian A. ;

Sanders, Rogier W. ;

Poignard, Pascal ;

Burton, Dennis R. .

IMMUNITY, 2014, 40 (05) :657-668

[18] Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization [J].

Georgiev, Ivelin S. ;

Doria-Rose, Nicole A. ;

Zhou, Tongqing ;

Do Kwon, Young ;

Staupe, Ryan P. ;

Moquin, Stephanie ;

Chuang, Gwo-Yu ;

Louder, Mark K. ;

Schmidt, Stephen D. ;

Altae-Tran, Han R. ;

Bailer, Robert T. ;

McKee, Krisha ;

Nason, Martha ;

O'Dell, Sijy ;

Ofek, Gilad ;

Pancera, Marie ;

Srivatsan, Sanjay ;

Shapiro, Lawrence ;

Connors, Mark ;

Migueles, Stephen A. ;

Morris, Lynn ;

Nishimura, Yoshiaki ;

Martin, Malcolm A. ;

Mascola, John R. ;

Kwong, Peter D. .

SCIENCE, 2013, 340 (6133) :751-756

[19] Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design [J].

Gorman, Jason ;

Soto, Cinque ;

Yang, Max M. ;

Davenport, Thaddeus M. ;

Guttman, Miklos ;

Bailer, Robert T. ;

Chambers, Michael ;

Chuang, Gwo-Yu ;

DeKosky, Brandon J. ;

Doria-Rose, Nicole A. ;

Druz, Aliaksandr ;

Ernandes, Michael J. ;

Georgiev, Ivelin S. ;

Jarosinski, Marissa C. ;

Joyce, M. Gordon ;

Lemmin, Thomas M. ;

Leung, Sherman ;

Louder, Mark K. ;

McDaniel, Jonathan R. ;

Narpala, Sandeep ;

Pancera, Marie ;

Stuckey, Jonathan ;

Wu, Xueling ;

Yang, Yongping ;

Zhang, Baoshan ;

Zhou, Tongqing ;

Mullikin, James C. ;

Baxa, Ulrich ;

Georgiou, George ;

McDermott, Adrian B. ;

Bonsignori, Mattia ;

Haynes, Barton F. ;

Moore, Penny L. ;

Morris, Lynn ;

Lee, Kelly K. ;

Shapiro, Lawrence ;

Mascola, John R. ;

Kwong, Peter D. .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2016, 23 (01) :81-90

[20] Natively glycosylated HIV-1 Env structure reveals new mode for antibody recognition of the CD4-binding site [J].

Gristick, Harry B. ;

von Boehmer, Lotta ;

West, Anthony P., Jr. ;

Schamber, Michael ;

Gazumyan, Anna ;

Golijanin, Jovana ;

Seaman, Michael S. ;

Faetkenheuer, Gerd ;

Klein, Florian ;

Nussenzweig, Michel C. ;

Bjorkman, Pamela J. .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2016, 23 (10) :906-915

← 1 2 3 4 5 6 →