A cytotoxic-skewed immune set point predicts low neutralizing antibody levels after Zika virus infection

被引：2

作者：

McCarthy, Elizabeth E. ^{[1
,2
]}

Odorizzi, Pamela M. ^{[3
,10
]}

Lutz, Emma ^{[3
]}

Smullin, Carolyn P. ^{[3
]}

Tenvooren, Iliana ^{[1
,2
]}

Stone, Mars ^{[4
,5
]}

Simmons, Graham ^{[4
,5
]}

Hunt, Peter W. ^{[3
]}

Feeney, Margaret E. ^{[3
,6
]}

Norris, Philip J. ^{[3
,4
,5
]}

Busch, Michael P. ^{[4
,5
]}

Matthew, H. ^{[1
,2
,7
,8
,9
]}

Rutishauser, Rachel L. ^{[3
,7
]}

机构：

[1] Univ Calif San Francisco, Dept Otolaryngol Head & Neck Surg, San Francisco, CA 94143 USA

[2] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA

[3] Univ Calif San Francisco, Zuckerberg San Francisco Gen Hosp, Dept Med, San Francisco, CA 94110 USA

[4] Vitalant Res Inst, San Francisco, CA 94104 USA

[5] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA

[6] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94110 USA

[7] Gladstone UCSF Inst Genom Immunol, San Francisco, CA 94158 USA

[8] Parker Inst Canc Immunotherapy, San Francisco, CA 94143 USA

[9] Chan Zuckerberg Biohub, San Francisco, CA 94158 USA

[10] Gilead Sci Inc, 353 Lakeside Dr, Foster City, CA 94404 USA

来源：

CELL REPORTS | 2022年 / 39卷 / 07期

基金：

美国国家卫生研究院;

关键词：

T-CELL RESPONSES; DENGUE VIRUS; R-PACKAGE; VACCINE; BLOOD; PERSISTENCE; CHALLENGE; EMERGENCE; SUBSETS; REVEALS;

D O I：

10.1016/j.celrep.2022.110815

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Although generating high neutralizing antibody levels is a key component of protective immunity after acute viral infection or vaccination, little is known about why some individuals generate high versus low neutralizing antibody titers. Here, we leverage the high-dimensional single-cell profiling capacity of mass cytometry to characterize the longitudinal cellular immune response to Zika virus (ZIKV) infection in viremic blood donors in Puerto Rico. During acute ZIKV infection, we identify widely coordinated responses across innate and adaptive immune cell lineages. High frequencies of multiple activated cell types during acute infection are associated with high titers of ZIKV neutralizing antibodies 6 months post-infection, while stable immune features suggesting a cytotoxic-skewed immune set point are associated with low titers. Our study offers insight into the coordination of immune responses and identifies candidate cellular biomarkers that may offer predictive value in vaccine efficacy trials aimed at inducing high levels of antiviral neutralizing antibodies.

引用

页数：21

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