High-resolution antibody dynamics of vaccine-induced immune responses

被引：128

作者：

Laserson, Uri ^{[1
,2
,3
]}

Vigneault, Francois ^{[2
,4
]}

Gadala-Maria, Daniel ^{[5
]}

Yaari, Gur ^{[6
]}

Uduman, Mohamed ^{[5
]}

Heiden, Jason A. Vander ^{[5
]}

Kelton, William ^{[7
]}

Jung, Sang Taek ^{[7
]}

Liu, Yi ^{[8
]}

Laserson, Jonathan ^{[8
]}

Chari, Raj ^{[2
]}

Lee, Je-Hyuk ^{[2
]}

Bachelet, Ido ^{[2
]}

Hickey, Brendan ^{[9
]}

Lieberman-Aiden, Erez ^{[10
]}

Hanczaruk, Bozena ^{[11
]}

Simen, Birgitte B. ^{[11
]}

Egholm, Michael ^{[11
]}

Koller, Daphne ^{[8
]}

Georgiou, George ^{[7
]}

Kleinstein, Steven H. ^{[5
,6
]}

Church, George M. ^{[1
,2
]}

机构：

[1] Harvard MIT Div Hlth Sci & Technol, Cambridge, MA 02139 USA

[2] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[3] MIT, Dept Math, Cambridge, MA 02139 USA

[4] AbVitro, Boston, MA 02210 USA

[5] Yale Univ, Interdept Program Computat Biol & Bioinformat, New Haven, CT 06520 USA

[6] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA

[7] Univ Texas Austin, Dept Chem Engn, Austin, TX 78712 USA

[8] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA

[9] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA

[10] Harvard Univ, Harvard Soc Fellows, Cambridge, MA 02138 USA

[11] 454 Life Sci, Branford, CT 06405 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2014年 / 111卷 / 13期

关键词：

next-generation sequencing; influenza; immunology; IMMUNOGLOBULIN; REPERTOIRE; SELECTION; DISCOVERY; LIBRARIES; DISEASE; MEMORY; HEAVY;

D O I：

10.1073/pnas.1323862111

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The adaptive immune system confers protection by generating a diverse repertoire of antibody receptors that are rapidly expanded and contracted in response to specific targets. Next-generation DNA sequencing now provides the opportunity to survey this complex and vast repertoire. In the present work, we describe a set of tools for the analysis of antibody repertoires and their application to elucidating the dynamics of the response to viral vaccination in human volunteers. By analyzing data from 38 separate blood samples across 2 y, we found that the use of the germ-line library of V and J segments is conserved between individuals over time. Surprisingly, there appeared to be no correlation between the use level of a particular VJ combination and degree of expansion. We found the antibody RNA repertoire in each volunteer to be highly dynamic, with each individual displaying qualitatively different response dynamics. By using combinatorial phage display, we screened selected VH genes paired with their corresponding VL library for affinity against the vaccine antigens. Altogether, this work presents an additional set of tools for profiling the human antibody repertoire and demonstrates characterization of the fast repertoire dynamics through time in multiple individuals responding to an immune challenge.

引用

页码：4928 / 4933

页数：6

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