Identification of Dengue Virus Serotype 3 Specific Antigenic Sites Targeted by Neutralizing Human Antibodies

被引：24

作者：

Young, Ellen ^{[1
]}

Carnahan, Robert H. ^{[2
]}

Andrade, Daniela, V ^{[4
]}

Kose, Nurgun ^{[3
]}

Nargi, Rachel S. ^{[3
]}

Fritch, Ethan J. ^{[6
]}

Munt, Jennifer E. ^{[1
]}

Doyle, Michael P. ^{[3
,5
]}

White, Laura ^{[6
]}

Baric, Thomas J. ^{[1
]}

Stoops, Mark ^{[6
]}

DeSilva, Aravinda ^{[6
]}

Tse, Longping, V ^{[1
]}

Martinez, David R. ^{[1
]}

Zhu, Deanna ^{[1
]}

Metz, Stefan ^{[6
]}

Wong, Marcus P. ^{[4
]}

Espinosa, Diego A. ^{[4
]}

Montoya, Magelda ^{[4
]}

Biering, Scott B. ^{[4
]}

Sukulpolvi-Petty, Soila ^{[7
]}

Kuan, Guillermina ^{[8
]}

Balmaseda, Angel ^{[9
]}

Diamond, Michael S. ^{[7
,10
,11
]}

Harris, Eva ^{[4
]}

Crowe, James E. ^{[2
,3
,5
]}

Baric, Ralph S. ^{[1
,6
]}

机构：

[1] Univ N Carolina, Dept Epidemiol, Gillings Sch Publ Hlth, Chapel Hill, NC 27515 USA

[2] Vanderbilt Univ, Med Ctr, Dept Pediat, Nashville, TN 37232 USA

[3] Vanderbilt Univ, Med Ctr, Vanderbilt Vaccine Ctr, Nashville, TN 37235 USA

[4] Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Vaccinol, Berkeley, CA 94720 USA

[5] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Nashville, TN 37235 USA

[6] Univ N Carolina, Dept Microbiol & Immunol, Sch Med, Chapel Hill, NC 27515 USA

[7] Washington Univ, Dept Med, Sch Med, St Louis, MO 63110 USA

[8] Minist Hlth, Hlth Ctr Socrates Flores Vivas, Managua, Nicaragua

[9] Minist Hlth, Natl Virol Lab, Natl Ctr Diag & Reference, Managua, Nicaragua

[10] Washington Univ, Sch Med, Mol Microbiol, St Louis, MO 63110 USA

[11] Washington Univ, Sch Med, Pathol & Immunol, St Louis, MO 63110 USA

来源：

CELL HOST & MICROBE | 2020年 / 27卷 / 05期

关键词：

MEMORY B-CELLS; MEDIATED NEUTRALIZATION; IMMUNE-RESPONSE; VACCINE; INFECTION; DISEASE; ENHANCEMENT; PROTECTION; IMPACTS; DIAGNOSIS;

D O I：

10.1016/j.chom.2020.04.007

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

The rational design of dengue virus (DENV) vaccines requires a detailed understanding of the molecular basis for antibody-mediated immunity. The durably protective antibody response to DENV after primary infection is serotype specific. However, there is an incomplete understanding of the antigenic determinants for DENV type-specific (TS) antibodies, especially for DENV serotype 3, which has only one well-studied, strongly neutralizing human monoclonal antibody (mAb). Here, we investigated the human B cell response in children after natural DENV infection in the endemic area of Nicaragua and isolated 15 DENV3 TS mAbs recognizing the envelope (E) glycoprotein. Functional epitope mapping of these mAbs and small animal prophylaxis studies revealed a complex landscape with protective epitopes clustering in at least 6-7 antigenic sites. Potently neutralizing TS mAbs recognized sites principally in E glycoprotein domains I and II, and patterns suggest frequent recognition of quaternary structures on the surface of viral particles.

引用

页码：710 / +

页数：22

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