HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogene

被引：343

作者：

Jardine, Joseph G. ^{[1
,2
,3
]}

Kulp, Daniel W. ^{[1
,2
,3
]}

Havenar-Daughton, Colin ^{[3
,4
]}

Sarkar, Anita ^{[2
,3
,5
]}

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

Sok, Devin ^{[1
,2
,3
]}

Sesterhenn, Fabian ^{[1
]}

Ereno-Orbea, June ^{[6
]}

Kalyuzhniy, Oleksandr ^{[1
,2
,3
]}

Deresa, Isaiah ^{[3
,4
]}

Hu, Xiaozhen ^{[1
,3
]}

Spencer, Skye ^{[1
,3
]}

Jones, Meaghan ^{[1
,3
]}

Georgeson, Erik ^{[1
,3
]}

Adachi, Yumiko ^{[1
,2
,3
]}

Kubitz, Michael ^{[1
,2
,3
]}

deCamp, Allan C. ^{[7
]}

Julien, Jean-Philippe ^{[2
,3
,5
,6
,8
,9
]}

Wilson, Ian A. ^{[2
,3
,5
,10
]}

Burton, Dennis R. ^{[1
,2
,3
,11
]}

Crotty, Shane ^{[3
,4
,12
]}

Schief, William R. ^{[1
,2
,3
,11
]}

机构：

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

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

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

[4] La Jolla Inst Allergy & Immunol, Div Vaccine Discovery, La Jolla, CA 92037 USA

[5] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[6] Hosp Sick Children, Res Inst, Program Mol Struct & Funct, Toronto, ON M5G 0A4, Canada

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

[8] Univ Toronto, Dept Biochem, Toronto, ON M5S 1A8, Canada

[9] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada

[10] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

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

[12] Univ Calif San Diego, Sch Med, Dept Med, Div Infect Dis, La Jolla, CA 92093 USA

来源：

SCIENCE | 2016年 / 351卷 / 6280期

关键词：

STRUCTURAL BASIS; RESPONSES; AFFINITY; REPERTOIRE; RECEPTORS; BINDING; DESIGN; SITE;

D O I：

10.1126/science.aad9195

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：

Induction of broadly neutralizing antibodies (bnAbs) is a major HIV vaccine goal. Germlinetargeting immunogens aim to initiate bnAb induction by activating bnAb germline precursor B cells. Critical unmet challenges are to determine whether bnAb precursor naive B cells bind germlinetargeting immunogens and occur at sufficient frequency in humans for reliable vaccine responses. Using deep mutational scanning and multitarget optimization, we developed a germlinetargeting immunogen (eODGT8) for diverse VRC01class bnAbs. We then used the immunogen to isolate VRC01class precursor naive B cells from HIVuninfected donors. Frequencies of true VRC01class precursors, their structures, and their eODGT8 affinities support this immunogen as a candidate human vaccine prime. These methods could be applied to germline targeting for other classes of HIV bnAbs and for Abs to other pathogens.

引用

页码：1458 / 1463

页数：6

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