Evaluation of candidate vaccine approaches for MERS-CoV

Lingshu Wang; Wei Shi; M. Gordon Joyce; Kayvon Modjarrad; Yi Zhang; Kwanyee Leung; Christopher R. Lees; Tongqing Zhou; Hadi M. Yassine; Masaru Kanekiyo; Zhi Yong Yang; Xuejun Chen; Michelle M. Becker; Megan Freeman; Leatrice Vogel; Joshua C. Johnson; Gene Olinger; John P. Todd; Ulas Bagci; Jeffrey Solomon; Daniel J. Mollura; Lisa Hensley; Peter Jahrling; Mark R. Denison; Srinivas S. Rao; Kanta Subbarao; Peter D. Kwong; John R. Mascola; Wing Pui Kong; Barney S. Graham

doi:10.1038/ncomms8712

Evaluation of candidate vaccine approaches for MERS-CoV

Lingshu Wang, Wei Shi, M. Gordon Joyce, Kayvon Modjarrad, Yi Zhang, Kwanyee Leung, Christopher R. Lees, Tongqing Zhou, Hadi M. Yassine, Masaru Kanekiyo, Zhi Yong Yang, Xuejun Chen, Michelle M. Becker, Megan Freeman, Leatrice Vogel, Joshua C. Johnson, Gene Olinger, John P. Todd, Ulas Bagci, Jeffrey SolomonDaniel J. Mollura, Lisa Hensley, Peter Jahrling, Mark R. Denison, Srinivas S. Rao, Kanta Subbarao, Peter D. Kwong, John R. Mascola, Wing Pui Kong, Barney S. Graham

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245 Scopus citations

Abstract

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 serum-neutralizing 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.

Original language	English (US)
Article number	7712
Journal	Nature communications
Volume	6
DOIs	https://doi.org/10.1038/ncomms8712
State	Published - Jul 28 2015
Externally published	Yes

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Wang, L., Shi, W., Joyce, M. G., Modjarrad, K., Zhang, Y., Leung, K., Lees, C. R., Zhou, T., Yassine, H. M., Kanekiyo, M., Yang, Z. Y., Chen, X., Becker, M. M., Freeman, M., Vogel, L., Johnson, J. C., Olinger, G., Todd, J. P., Bagci, U., ... Graham, B. S. (2015). Evaluation of candidate vaccine approaches for MERS-CoV. Nature communications, 6, Article 7712. https://doi.org/10.1038/ncomms8712

Wang, L, Shi, W, Joyce, MG, Modjarrad, K, Zhang, Y, Leung, K, Lees, CR, Zhou, T, Yassine, HM, Kanekiyo, M, Yang, ZY, Chen, X, Becker, MM, Freeman, M, Vogel, L, Johnson, JC, Olinger, G, Todd, JP, Bagci, U, Solomon, J, Mollura, DJ, Hensley, L, Jahrling, P, Denison, MR, Rao, SS, Subbarao, K, Kwong, PD, Mascola, JR, Kong, WP & Graham, BS 2015, 'Evaluation of candidate vaccine approaches for MERS-CoV', Nature communications, vol. 6, 7712. https://doi.org/10.1038/ncomms8712

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title = "Evaluation of candidate vaccine approaches for MERS-CoV",

abstract = "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 serum-neutralizing 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.",

author = "Lingshu Wang and Wei Shi and Joyce, {M. Gordon} and Kayvon Modjarrad and Yi Zhang and Kwanyee Leung and Lees, {Christopher R.} and Tongqing Zhou and Yassine, {Hadi M.} and Masaru Kanekiyo and Yang, {Zhi Yong} and Xuejun Chen and Becker, {Michelle M.} and Megan Freeman and Leatrice Vogel and Johnson, {Joshua C.} and Gene Olinger and Todd, {John P.} and Ulas Bagci and Jeffrey Solomon and Mollura, {Daniel J.} and Lisa Hensley and Peter Jahrling and Denison, {Mark R.} and Rao, {Srinivas S.} and Kanta Subbarao and Kwong, {Peter D.} and Mascola, {John R.} and Kong, {Wing Pui} and Graham, {Barney S.}",

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AU - Joyce, M. Gordon

AU - Modjarrad, Kayvon

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AU - Leung, Kwanyee

AU - Lees, Christopher R.

AU - Zhou, Tongqing

AU - Yassine, Hadi M.

AU - Kanekiyo, Masaru

AU - Yang, Zhi Yong

AU - Chen, Xuejun

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AU - Freeman, Megan

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AU - Olinger, Gene

AU - Todd, John P.

AU - Bagci, Ulas

AU - Solomon, Jeffrey

AU - Mollura, Daniel J.

AU - Hensley, Lisa

AU - Jahrling, Peter

AU - Denison, Mark R.

AU - Rao, Srinivas S.

AU - Subbarao, Kanta

AU - Kwong, Peter D.

AU - Mascola, John R.

AU - Kong, Wing Pui

AU - Graham, Barney S.

PY - 2015/7/28

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N2 - 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 serum-neutralizing 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.

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Evaluation of candidate vaccine approaches for MERS-CoV

Abstract

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