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

Nature Communications 6, article 77122015

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Conceptual illustration of coronavirus Spike protein and DNA- and protein-based vaccine approaches in a preclinical study. — Generated with OpenAI gpt-image-2.5-sunburst Conceptual illustration.

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.

Abstract source

This 2015 study evaluated DNA- and protein-based MERS-CoV vaccine candidates in mice and rhesus macaques. The authors report neutralizing antibody responses and protection from radiographic pneumonia in macaques; the findings are preclinical.

Summary

The study compared vaccine regimens based on MERS-CoV Spike protein, including DNA immunization and protein subunits. The authors assessed antibody responses in mice and non-human primates, and evaluated selected regimens in rhesus macaques challenged with MERS-CoV. They report that a regimen combining Spike DNA with S1 protein elicited neutralizing antibodies and protected macaques from MERS-CoV-induced radiographic pneumonia. These are animal-study findings, not evidence of efficacy or readiness for use in humans. Read the full article.

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