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Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus

引用

Cellular & Molecular Immunology 2016年第2期13卷 180-190页

作者： Naru Zhang rudragouda channappanavar Cuiqing Ma Lili Wang Jian Tang Tania Garron Xinrong Tao Sumaiya Tasneem Lu Lu Chien-Te K Tseng Yusen Zhou Stanley Perlman Shibo Jiang Lanying Du Lindsley F. Kimball Research Institute New York Blood Center New York NY USA Department of Microbiology University of Iowa Iowa City IA USA State Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and Epidemiology Beijing China Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease University of Texas Medical Branch Galveston TX USA Key Laboratory of Medical Molecular Virology of Ministries of Education and Health Shanghai Medical College and Institute of Medical Microbiology Fudan University Shanghai China Xiang-Ya Medical College Central South University Changsha. China

Middle East respiratory syndrome （MERS）, an emerging infectious disease caused by MERS coronavirus （MERS-CoV）, has garnered worldwide attention as a consequence of its continuous spread and pandemic potential, making the development of effective vaccines a high priority. We previously demonstrated that residues 377-588 of MERS-CoV spike （S） protein receptor-binding domain （RBD） is a very promising MERS subunit vaccine candidate, capable of inducing potent neutralization antibody responses. In this study, we sought to identify an adjuvant that optimally enhanced the immunogenicity of S377-588 protein fused with Fc of human IgG （S377-588-Fc）. Specifically, we compared several commercially available adjuvants, including Freund＇s adjuvant, aluminum, Monophosphoryl lipid A, Montanide ISA51 and MF59 with regard to their capacity to enhance the immunogenicity of this subunit vaccine. In the absence of adjuvant, S377-588-Fc alone induced readily detectable neutralizing antibody and T-cell responses in immunized mice. However, incorporating an adjuvant improved its immunogenicity. Particularly, among the aforementioned adjuvants evaluated, MF59 is the most potent as judged by its superior ability to induce the highest titers of IgG, IgG1 and IgG2a subtypes, and neutralizing antibodies. The addition of MF59 significantly augmented the immunogenicity of S377-588-Fcto induce strong IgG and neutralizing antibody responses as well as protection against MERS-CoV infection in mice, suggesting that MF59 is an optimal adjuvant for MERS-CoV RBD-based subunit vaccines.

关键词： adjuvant effects MERS MERS-CoV receptor-binding domain subunit vaccine

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