Immunization for HIV-1 Broadly Neutralizing Antibodies in Human Ig Knockin Mice

被引：214

作者：

Dosenovic, Pia ^{[1
]}

von Boehmer, Lotta ^{[1
]}

Escolano, Amelia ^{[1
]}

Jardine, Joseph ^{[3
,10
,11
]}

Freund, Natalia T. ^{[1
]}

Gitlin, Alexander D. ^{[1
]}

McGuire, Andrew T. ^{[4
]}

Kulp, Daniel W. ^{[3
,10
,11
]}

Oliveira, Thiago ^{[1
]}

Scharf, Louise ^{[5
]}

Pietzsch, John ^{[1
]}

Gray, Matthew D. ^{[4
]}

Cupo, Albert ^{[6
]}

van Gils, Marit J. ^{[7
]}

Yao, Kai-Hui ^{[1
]}

Liu, Cassie ^{[1
]}

Gazumyan, Anna ^{[1
,2
]}

Seaman, Michael S. ^{[8
]}

Bjoerkman, Pamela J. ^{[2
,5
]}

Sanders, Rogier W. ^{[6
]}

Moore, John P. ^{[6
]}

Stamatatos, Leonidas ^{[4
,9
]}

Schief, William R. ^{[3
,10
,11
,12
]}

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

机构：

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

[2] Scripps Res Inst, Howard Hughes Med Inst, La Jolla, CA 92037 USA

[3] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[4] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA

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

[6] Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10065 USA

[7] Univ Amsterdam, Acad Med Ctr, Dept Med Microbiol, NL-1105 AZ Amsterdam, Netherlands

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

[9] Univ Washington, Dept Global Hlth, Seattle, WA 98109 USA

[10] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA

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

[12] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02129 USA

来源：

CELL | 2015年 / 161卷 / 07期

基金：

欧洲研究理事会; 加拿大健康研究院; 瑞典研究理事会;

关键词：

B-CELL RECEPTORS; ENVELOPE TRIMER; SOMATIC HYPERMUTATION; VACCINE; VIRUS; GP120; SITE; RECOMBINATION; GLYCOPROTEIN; AFFINITY;

D O I：

10.1016/j.cell.2015.06.003

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：

A subset of individuals infected with HIV-1 develops broadly neutralizing antibodies (bNAbs) that can prevent infection, but it has not yet been possible to elicit these antibodies by immunization. To systematically explore how immunization might be tailored to produce them, we generated mice expressing the predicted germline or mature heavy chains of a potent bNAb to the CD4 binding site (CD4bs) on the HIV-1 envelope glycoprotein (Env). Immunogens specifically designed to activate B cells bearing germline antibodies are required to initiate immune responses, but they do not elicit bNAbs. In contrast, native-like Env trimers fail to activate B cells expressing germline antibodies but elicit bNAbs by selecting for a restricted group of light chains bearing specific somatic mutations that enhance neutralizing activity. The data suggest that vaccination to elicit anti-HIV-1 antibodies will require immunization with a succession of related immunogens.

引用

页码：1505 / 1515

页数：11

共 42 条

[11] Crystal Structure of a Soluble Cleaved HIV-1 Envelope Trimer
Julien, Jean-Philippe
Cupo, Albert
Sok, Devin
Stanfield, Robyn L.
Lyumkis, Dmitry
Deller, Marc C.
Klasse, Per-Johan
Burton, Dennis R.
Sanders, Rogier W.
Moore, John P.
Ward, Andrew B.
Wilson, Ian A.
[J]. SCIENCE, 2013, 342 (6165) : 1477 - 1483
[12] The Thai Phase III HIV Type 1 Vaccine Trial (RV144) Regimen Induces Antibodies That Target Conserved Regions Within the V2 Loop of gp120
Karasavvas, Nicos
Billings, Erik
Rao, Mangala
Williams, Constance
Zolla-Pazner, Susan
Bailer, Robert T.
Koup, Richard A.
Madnote, Sirinan
Arworn, Duangnapa
Shen, Xiaoying
Tomaras, Georgia D.
Currier, Jeffrey R.
Jiang, Mike
Magaret, Craig
Andrews, Charla
Gottardo, Raphael
Gilbert, Peter
Cardozo, Timothy J.
Rerks-Ngarm, Supachai
Nitayaphan, Sorachai
Pitisuttithum, Punnee
Kaewkungwal, Jaranit
Paris, Robert
Greene, Kelli
Gao, Hongmei
Gurunathan, Sanjay
Tartaglia, Jim
Sinangil, Faruk
Korber, Bette T.
Montefiori, David C.
Mascola, John R.
Robb, Merlin L.
Haynes, Barton F.
Ngauy, Viseth
Michael, Nelson L.
Kim, Jerome H.
de Souza, Mark S.
[J]. AIDS RESEARCH AND HUMAN RETROVIRUSES, 2012, 28 (11) : 1444 - 1457
[13] Enhanced HIV-1 immunotherapy by commonly arising antibodies that target virus escape variants
Klein, Florian
Nogueira, Lilian
Nishimura, Yoshiaki
Phad, Ganesh
West, Anthony P., Jr.
Halper-Stromberg, Ariel
Horwitz, Joshua A.
Gazumyan, Anna
Liu, Cassie
Eisenreich, Thomas R.
Lehmann, Clara
Faetkenheuer, Gerd
Williams, Constance
Shingai, Masashi
Martin, Malcolm A.
Bjorkman, Pamela J.
Seaman, Michael S.
Zolla-Pazner, Susan
Hedestam, Gunilla B. Karlsson
Nussenzweig, Michel C.
[J]. JOURNAL OF EXPERIMENTAL MEDICINE, 2014, 211 (12) : 2361 - 2372
[14] Antibodies in HIV-1 Vaccine Development and Therapy
Klein, Florian
Mouquet, Hugo
Dosenovic, Pia
Scheid, Johannes F.
Scharf, Louise
Nussenzweig, Michel C.
[J]. SCIENCE, 2013, 341 (6151) : 1199 - 1204
[15] Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody
Kwong, PD
Wyatt, R
Robinson, J
Sweet, RW
Sodroski, J
Hendrickson, WA
[J]. NATURE, 1998, 393 (6686) : 648 - 659
[16] Leaver-Fay A, 2011, METHOD ENZYMOL, P545, DOI [10.1016/S0076-6879(11)87019-9, 10.1016/B978-0-12-381270-4.00019-6]
[17] Human immunodeficiency virus type 1 env clones from acute and early subtype B infections for standardized assessments of vaccine-elicited neutralizing antibodies
Li, M
Gao, F
Mascola, JR
Stamatatos, L
Polonis, VR
Koutsoukos, M
Voss, G
Goepfert, P
Gilbert, P
Greene, KM
Bilska, M
Kothe, DL
Salazar-Gonzalez, JF
Wei, XP
Decker, JM
Hahn, BH
Montefiori, DC
[J]. JOURNAL OF VIROLOGY, 2005, 79 (16) : 10108 - 10125
[18] Harnessing homologous recombination in vitro to generate recombinant DNA via SLIC
Li, Mamie Z.
Elledge, Stephen J.
[J]. NATURE METHODS, 2007, 4 (03) : 251 - 256
[19] Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus
Liao, Hua-Xin
Lynch, Rebecca
Zhou, Tongqing
Gao, Feng
Alam, S. Munir
Boyd, Scott D.
Fire, Andrew Z.
Roskin, Krishna M.
Schramm, Chaim A.
Zhang, Zhenhai
Zhu, Jiang
Shapiro, Lawrence
Mullikin, James C.
Gnanakaran, S.
Hraber, Peter
Wiehe, Kevin
Kelsoe, Garnett
Yang, Guang
Xia, Shi-Mao
Montefiori, David C.
Parks, Robert
Lloyd, Krissey E.
Scearce, Richard M.
Soderberg, Kelly A.
Cohen, Myron
Kamanga, Gift
Louder, Mark K.
Tran, Lillian M.
Chen, Yue
Cai, Fangping
Chen, Sheri
Moquin, Stephanie
Du, Xiulian
Joyce, M. Gordon
Srivatsan, Sanjay
Zhang, Baoshan
Zheng, Anqi
Shaw, George M.
Hahn, Beatrice H.
Kepler, Thomas B.
Korber, Bette T. M.
Kwong, Peter D.
Mascola, John R.
Haynes, Barton F.
[J]. NATURE, 2013, 496 (7446) : 469 - +
[20] AID in somatic hypermutation and class switch recombination
Longerich, S
Basu, U
Alt, F
Storb, U
[J]. CURRENT OPINION IN IMMUNOLOGY, 2006, 18 (02) : 164 - 174

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