title: Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus.
abstract: 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-Fc to 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.
authors: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
authors: Naru
authors: N
authors: Zhang
authors: Department of Microbiology, University of Iowa, Iowa City, IA, USA.
authors: Rudragouda
authors: R
authors: Channappanavar
authors: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
authors: Cuiqing
authors: C
authors: Ma
authors: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
authors: Lili
authors: L
authors: Wang
authors: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.|State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.|Xiang-Ya Medical College, Central South University, Changsha, China.
authors: Jian
authors: J
authors: Tang
authors: Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA.
authors: Tania
authors: T
authors: Garron
authors: Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA.
authors: Xinrong
authors: X
authors: Tao
authors: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
authors: Sumaiya
authors: S
authors: Tasneem
authors: Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai, Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China.
authors: Lu
authors: L
authors: Lu
authors: Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA.
authors: Chien-Te K
authors: CT
authors: Tseng
authors: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China.|Xiang-Ya Medical College, Central South University, Changsha, China.
authors: Yusen
authors: Y
authors: Zhou
authors: Department of Microbiology, University of Iowa, Iowa City, IA, USA.
authors: Stanley
authors: S
authors: Perlman
authors: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, 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.
authors: Shibo
authors: S
authors: Jiang
authors: Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA.
authors: Lanying
authors: L
authors: Du
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D018352:Coronavirus Infections / Q000276:immunology / Q000517:prevention & control; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D065207:Middle East Respiratory Syndrome Coronavirus / Q000276:immunology*; D064370:Spike Glycoprotein, Coronavirus / Q000276:immunology / Q000494:pharmacology*; D022223:Vaccines, Subunit / Q000276:immunology / Q000494:pharmacology; D014765:Viral Vaccines / Q000276:immunology / Q000493:pharmacokinetics*
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007074:Immunoglobulin G; D064370:Spike Glycoprotein, Coronavirus; D022223:Vaccines, Subunit; D014765:Viral Vaccines
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