Protein nanoparticle vaccines induce potent neutralizing antibody responses against MERS-CoV

被引：3

作者：

Chao, Cara W. ^{[1
,2
,3
]}

Sprouse, Kaitlin R. ^{[2
]}

Miranda, Marcos C. ^{[1
,2
,9
]}

Catanzaro, Nicholas J. ^{[4
]}

Hubbard, Miranda L. ^{[4
]}

Addetia, Amin ^{[2
]}

Stewart, Cameron ^{[2
]}

Brown, Jack T. ^{[2
]}

Dosey, Annie ^{[1
,2
]}

Valdez, Adian ^{[1
,2
]}

Ravichandran, Rashmi ^{[1
,2
]}

Hendricks, Grace G. ^{[1
,2
]}

Ahlrichs, Maggie ^{[1
,2
]}

Dobbins, Craig ^{[1
,2
]}

Hand, Alexis ^{[1
,2
,10
]}

Mcgowan, Jackson ^{[1
,2
,6
]}

Simmons, Boston ^{[1
,2
]}

Treichel, Catherine ^{[1
,2
,11
]}

Willoughby, Isabelle ^{[1
,2
]}

Walls, Alexandra C. ^{[2
,4
]}

Mcguire, Andrew T. ^{[2
,7
,8
]}

Leaf, Elizabeth M. ^{[1
,2
]}

Baric, Ralph S. ^{[4
]}

Schafer, Alexandra ^{[4
]}

Veesler, David ^{[2
,5
]}

King, Neil P. ^{[1
,2
]}

机构：

[1] Univ Washington, Inst Prot Design, Seattle, WA 98195 USA

[2] Univ Washington, Dept Biochem, Seattle, WA 98195 USA

[3] Univ Washington, Grad Program Mol & Cellular Biol, Seattle, WA 98195 USA

[4] Univ North Carolina Chapel Hill, Dept Epidemiol, Chapel Hill, NC 27514 USA

[5] Howard Hughes Med Inst, Seattle, WA 98195 USA

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

[7] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA

[8] Univ Washington, Dept Lab Med, Seattle, WA 98115 USA

[9] Washington Univ St Louis, St Louis, MO USA

[10] Mayo Clin Arizona, Phoenix, AZ USA

[11] Univ Bristol, Bristol, England

来源：

CELL REPORTS | 2024年 / 43卷 / 12期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

RECEPTOR-BINDING DOMAIN; EFFECTOR FUNCTIONS; IMMUNOGEN DESIGN; GLYCOPROTEIN; IDENTIFICATION; CORONAVIRUSES; VISUALIZATION;

D O I：

10.1016/j.celrep.2024.115036

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Middle East respiratory syndrome coronavirus (MERS-CoV) is a betacoronavirus that causes severe respiratory illness in humans. There are no licensed vaccines against MERS-CoV and only a few candidates in phase I clinical trials. Here, we develop MERS-CoV vaccines utilizing a computationally designed protein nanoparticle platform that has generated safe and immunogenic vaccines against various enveloped viruses, including licensed vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Two-component nano particles displaying spike (S)-derived antigens induce neutralizing responses and protect mice against challenge with mouse-adapted MERS-CoV. Epitope mapping reveals the dominant responses elicited by immunogens displaying the prefusion-stabilized S-2P trimer, receptor binding domain (RBD), or N-terminal domain (NTD). An RBD nanoparticle elicits antibodies targeting multiple non-overlapping epitopes in the RBD. Our findings demonstrate the potential of two-component nanoparticle vaccine candidates for MERS-CoV and suggest that this platform technology could be broadly applicable to betacoronavirus vaccine development.

引用

页数：20

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