Evaluation of candidate vaccine approaches for MERS-CoV

被引：213

作者：

Wang, Lingshu ^{[1
]}

Shi, Wei ^{[1
]}

Joyce, M. Gordon ^{[1
]}

Modjarrad, Kayvon ^{[1
,2
,3
]}

Zhang, Yi ^{[1
]}

Leung, Kwanyee ^{[1
]}

Lees, Christopher R. ^{[1
]}

Zhou, Tongqing ^{[1
]}

Yassine, Hadi M. ^{[1
]}

Kanekiyo, Masaru ^{[1
]}

Yang, Zhi-yong ^{[1
,4
]}

Chen, Xuejun ^{[1
]}

Becker, Michelle M. ^{[5
]}

Freeman, Megan ^{[5
]}

Vogel, Leatrice ^{[6
]}

Johnson, Joshua C. ^{[7
]}

Olinger, Gene ^{[7
]}

Todd, John P. ^{[1
]}

Bagci, Ulas ^{[8
,9
]}

Solomon, Jeffrey ^{[8
]}

Mollura, Daniel J. ^{[8
]}

Hensley, Lisa ^{[7
]}

Jahrling, Peter ^{[7
]}

Denison, Mark R. ^{[5
,10
]}

Rao, Srinivas S. ^{[1
]}

Subbarao, Kanta ^{[6
]}

Kwong, Peter D. ^{[1
]}

Mascola, John R. ^{[1
]}

Kong, Wing-Pui ^{[1
]}

Graham, Barney S. ^{[1
]}

机构：

[1] NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA

[2] US Mil HIV Res Program, Walter Reed Army Inst Res, Silver Spring, MD 20910 USA

[3] Henry M Jackson Fdn Adv Mil Med, Bethesda, MD 20817 USA

[4] Sanofi Aventis, Cambridge, MA 02139 USA

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

[6] NIAID, Emerging Resp Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA

[7] NIAID, Integrated Res Facil, NIH, Frederick, MD 21702 USA

[8] NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA

[9] Univ Cent Florida, CRCV, Orlando, FL 32816 USA

[10] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Med Ctr, Nashville, TN 37232 USA

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

关键词：

RESPIRATORY SYNDROME CORONAVIRUS; RECEPTOR-BINDING DOMAIN; IMMUNE-RESPONSES; SPIKE PROTEIN; NEUTRALIZING ANTIBODIES; SAUDI-ARABIA; GLYCOPROTEIN; MICE; IMMUNOGENICITY; IMMUNIZATION;

D O I：

10.1038/ncomms8712

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：

The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV) as a cause of severe respiratory disease highlights the need for effective approaches to CoV vaccine development. Efforts focused solely on the receptor-binding domain (RBD) of the viral Spike (S) glycoprotein may not optimize neutralizing antibody (NAb) responses. Here we show that immunogens based on full-length S DNA and S1 subunit protein elicit robust serumneutralizing activity against several MERS-CoV strains in mice and non-human primates. Serological analysis and isolation of murine monoclonal antibodies revealed that immunization elicits NAbs to RBD and, non-RBD portions of S1 and S2 subunit. Multiple neutralization mechanisms were demonstrated by solving the atomic structure of a NAb-RBD complex, through sequencing of neutralization escape viruses and by constructing MERS-CoV S variants for serological assays. Immunization of rhesus macaques confers protection against MERS-CoV-induced radiographic pneumonia, as assessed using computerized tomography, supporting this strategy as a promising approach for MERS-CoV vaccine development.

引用

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