Germline-Encoded Affinity for Cognate Antigen Enables Vaccine Amplification of a Human Broadly Neutralizing Response against Influenza Virus

被引：62

作者：

Sangesland, Maya ^{[1
,2
]}

Ronsard, Larance ^{[1
,2
]}

Kazer, Samuel W. ^{[1
,2
,3
,4
,5
,6
]}

Bals, Julia ^{[1
,2
]}

Boyoglu-Barnum, Seyhan ^{[7
]}

Yousif, Ashraf S. ^{[1
,2
]}

Barnes, Ralston ^{[8
]}

Feldman, Jared ^{[1
,2
]}

Quirindongo-Crespo, Maricel ^{[8
]}

McTamney, Patrick M. ^{[9
]}

Rohrer, Daniel ^{[8
]}

Lonberg, Nils ^{[8
]}

Chackerian, Bryce ^{[10
]}

Graham, Barney S. ^{[7
]}

Kanekiyo, Masaru ^{[7
]}

Shalek, Alex K. ^{[1
,2
,3
,4
,5
,6
]}

Lingwood, Daniel ^{[1
,2
]}

机构：

[1] MIT, Massachusetts Gen Hosp, Ragon Inst, 400 Technol Sq, Cambridge, MA 02139 USA

[2] Harvard Univ, 400 Technol Sq, Cambridge, MA 02139 USA

[3] MIT, Dept Chem, IMES, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[4] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[5] MIT, Broad Inst, 415 Main St, Cambridge, MA 02142 USA

[6] Harvard Univ, 415 Main St, Cambridge, MA 02142 USA

[7] NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA

[8] Bristol Myers Squibb, 700 Bay Rd, Redwood City, CA 94063 USA

[9] Medimmune LLC, One Medimmune Way, Gaithersburg, MD 20878 USA

[10] Univ New Mexico, Sch Med, Dept Mol Genet & Microbiol, 2425 Camino Salud, Albuquerque, NM 87106 USA

来源：

IMMUNITY | 2019年 / 51卷 / 04期

关键词：

MEMORY B-CELLS; HEMAGGLUTININ-STEM; HUMAN-ANTIBODIES; HIV; IMMUNIZATION; MICE; IMMUNITY; REPERTOIRE; PRECURSORS; EXPRESSION;

D O I：

10.1016/j.immuni.2019.09.001

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 paratopes are formed by hypervariable complementarity-determining regions (CDRH3s) and variable gene-encoded CDRs. The latter show biased usage in human broadly neutralizing antibodies (bnAbs) against both HIV and influenza virus, suggesting the existence of gene-endowed targeting solutions that may be amenable to pathway amplification. To test this, we generated transgenic mice with human CDRH3 diversity but simultaneously constrained to individual user-defined human immunoglobulin variable heavy-chain (V-H) genes, including IGHV1-69, which shows biased usage in human bnAbs targeting the hemagglutinin stalk of group 1 influenza A viruses. Sequential immunization with a stalk-only hemagglutinin nanoparticle elicited group 1 bnAbs, but only in IGHV1-69 mice. This V-H-endowed response required minimal affinity maturation, was elicited alongside pre-existing influenza immunity, and when IGHV1-69 B cells were diluted to match the frequency measured in humans. These results indicate that the human repertoire could, in principle, support germline-encoded bnAb elicitation using a single recombinant hemagglutinin immunogen.

引用

页码：735 / +

页数：23

共 81 条

[11] Implications of broadly neutralizing antibodies in the development of a universal influenza vaccine [J].

Cho, Alice ;

Wrammert, Jens .

CURRENT OPINION IN VIROLOGY, 2016, 17 :110-115

[12] THE PROTECTON - THE UNIT OF HUMORAL IMMUNITY SELECTED BY EVOLUTION [J].

COHN, M ;

LANGMAN, RE .

IMMUNOLOGICAL REVIEWS, 1990, 115 :7-147

[13] WebLogo: A sequence logo generator [J].

Crooks, GE ;

Hon, G ;

Chandonia, JM ;

Brenner, SE .

GENOME RESEARCH, 2004, 14 (06) :1188-1190

[14] A Public Database of Memory and Naive B-Cell Receptor Sequences [J].

DeWitt, William S. ;

Lindau, Paul ;

Snyder, Thomas M. ;

Sherwood, Anna M. ;

Vignali, Marissa ;

Carlson, Christopher S. ;

Greenberg, Philip D. ;

Duerkopp, Natalie ;

Emerson, Ryan O. ;

Robins, Harlan S. .

PLOS ONE, 2016, 11 (08)

[15] Broadly neutralizing anti-influenza antibodies require Fc receptor engagement for in vivo protection [J].

DiLillo, David J. ;

Palese, Peter ;

Wilson, Patrick C. ;

Ravetch, Jeffrey V. .

JOURNAL OF CLINICAL INVESTIGATION, 2016, 126 (02) :605-610

[16] Broadly neutralizing hemagglutinin stalk-specific antibodies require FcγR interactions for protection against influenza virus in vivo [J].

DiLillo, David J. ;

Tan, Gene S. ;

Palese, Peter ;

Ravetch, Jeffrey V. .

NATURE MEDICINE, 2014, 20 (02) :143-151

[17] Anti-idiotypic antibodies elicit anti-HIV-1-specific B cell responses [J].

Dosenovic, Pia ;

Pettersson, Anna-Klara ;

Wall, Abigail ;

Thientosapol, Eddy S. ;

Feng, Junli ;

Weidle, Connor ;

Bhullar, Komal ;

Kara, Ervin E. ;

Hartweger, Harald ;

Pai, Joy A. ;

Gray, Matthew D. ;

Parks, K. Rachael ;

Taylor, Justin J. ;

Pancera, Marie ;

Stamatatos, Leonidas ;

Nussenzweig, Michel C. ;

McGuire, Andrew T. .

JOURNAL OF EXPERIMENTAL MEDICINE, 2019, 216 (10) :2316-2330

[18] Anti-HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity [J].

Dosenovic, Pia ;

Kara, Ervin E. ;

Pettersson, Anna-Klara ;

McGuire, Andrew T. ;

Gray, Matthew ;

Hartweger, Harald ;

Thientosapol, Eddy S. ;

Stamatatos, Leonidas ;

Nussenzweig, Michel C. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2018, 115 (18) :4743-4748

[19] 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

[20] Glycan Masking Focuses Immune Responses to the HIV-1 CD4-Binding Site and Enhances Elicitation of VRC01-Class Precursor Antibodies [J].

Duan, Hongying ;

Chen, Xuejun ;

Boyington, Jeffrey C. ;

Cheng, Cheng ;

Zhang, Yi ;

Jafari, Alexander J. ;

Stephens, Tyler ;

Tsybovsky, Yaroslav ;

Kalyuzhniy, Oleksandr ;

Zhao, Peng ;

Menis, Sergey ;

Nason, Martha C. ;

Normandin, Erica ;

Mukhamedova, Maryam ;

DeKosky, Brandon J. ;

Wells, Lance ;

Schief, William R. ;

Tian, Ming ;

Alt, Frederick W. ;

Kwong, Peter D. ;

Mascola, John R. .

IMMUNITY, 2018, 49 (02) :301-+

← 1 2 3 4 5 6 7 8 9 →