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Evaluation of candidate vaccine approaches for MERS-CoV
Open accessAbstract
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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Metadata
- Authors
- 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., Solomon, J., Mollura, D. J., Hensley, L., Jahrling, P., Denison, M. R., Rao, S. S., Subbarao, K., Kwong, P. D., Mascola, J. R., Kong, W.-P., & Graham, B. S.
- Venue
- Nature Communications
- Published
- 2015-07-28
- Volume
- 6
- Issue
- 1
- Pages
- 7712-7712
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W2270879391
- Cited by
- 299
- References
- 50
- FWCI
- 17.83
- Type
- journal article
- Language
- en
- Open access
- gold
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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. https://doi.org/10.1038/ncomms8712
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