Direct Probing of Germinal Center Responses Reveals Immunological Features and Bottlenecks for Neutralizing Antibody Responses to HIV Env Trimer

被引：143

作者：

Havenar-Daughton, Colin ^{[1
,2
]}

Carnathan, Diane G. ^{[2
,3
]}

de la Pena, Alba Torrents ^{[5
]}

Pauthner, Matthias ^{[2
,4
]}

Briney, Bryan ^{[2
,4
]}

Reiss, Samantha M. ^{[1
,2
]}

Wood, Jennifer S. ^{[3
]}

Kaushik, Kirti ^{[1
,2
]}

van Gils, Marit J. ^{[5
]}

Rosales, Sandy L. ^{[1
]}

van der Woude, Patricia ^{[5
]}

Locci, Michela ^{[1
,2
]}

Le, Khoa M. ^{[2
,4
]}

de Taeye, Steven W. ^{[5
]}

Sok, Devin ^{[2
,4
]}

Mohammed, Ata Ur Rasheed ^{[6
]}

Huang, Jessica ^{[6
]}

Gumber, Sanjeev ^{[3
]}

Garcia, AnaPatricia ^{[3
]}

Kasturi, Sudhir P. ^{[3
,6
]}

Pulendran, Bali ^{[2
,3
,6
]}

Moore, John P. ^{[7
]}

Ahmed, Rafi ^{[2
,6
]}

Seumois, Gregory ^{[1
]}

Burton, Dennis R. ^{[2
,4
,9
,10
]}

Sanders, Rogier W. ^{[5
,7
]}

Silvestri, Guido ^{[2
,3
,6
]}

Crotty, Shane ^{[1
,2
,8
]}

机构：

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

[2] Scripps Ctr HIV AIDS Vaccine Immunol & Immunogen, La Jolla, CA 92037 USA

[3] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA

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

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

[6] Emory Univ, Sch Med, Emory Vaccine Ctr, Atlanta, GA 30322 USA

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

[8] Univ Calif San Diego, Div Infect Dis, Dept Med, La Jolla, CA 92037 USA

[9] MIT, MGH, Ragon Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[10] Harvard, Cambridge, MA 02139 USA

来源：

CELL REPORTS | 2016年 / 17卷 / 09期

基金：

欧洲研究理事会;

关键词：

FINE-NEEDLE-ASPIRATION; FOLLICULAR HELPER-CELLS; CRYO-EM STRUCTURE; CD4(+) T-CELLS; ENVELOPE TRIMERS; LYMPH-NODE; MEMORY; PROTECTION; DIFFERENTIATION; IMMUNOGENICITY;

D O I：

10.1016/j.celrep.2016.10.085

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Generating tier 2 HIV-neutralizing antibody (nAb) responses by immunization remains a challenging problem, and the immunological barriers to induction of such responses with Env immunogens remain unclear. Here, some rhesus monkeys developed autologous tier 2 nAbs upon HIV Env trimer immunization (SOSIP.v5.2) whereas others did not. This was not because HIV Env trimers were immunologically silent because all monkeys made similar ELISA-binding antibody responses; the key difference was nAb versus non-nAb responses. We explored the immunological barriers to HIV nAb responses by combining a suite of techniques, including longitudinal lymph node fine needle aspirates. Unexpectedly, nAb development best correlated with booster immunization GC B cell magnitude and Tfh characteristics of the Env-specific CD4 T cells. Notably, these factors distinguished between successful and un-successful antibody responses because GC B cell frequencies and stoichiometry to GC Tfh cells-correlated with nAb development, but did not correlate with total Env Ab binding titers.

引用

页码：2195 / 2209

页数：15

共 61 条

[1] Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design [J].