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

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

doi:10.1038/cmi.2015.03

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

Journal article

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

Naru Zhang, Rudragouda Channappanavar, Cuiqing Ma, Lili Wang, Jian Tang, Tania Garron, Xinrong Tao, Sumaiya Tasneem, Lu Lu, Chien-Te K Tseng, …

Cellular & molecular immunology, Vol.13(2), pp.180-190

03/2016

DOI: 10.1038/cmi.2015.03

PMCID: PMC4786625

PMID: 25640653

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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.

Coronavirus Infections - prevention & control

Adjuvants, Immunologic - pharmacology

Humans

Vaccines, Subunit - immunology

Coronavirus Infections - immunology

Middle East Respiratory Syndrome Coronavirus - immunology

Viral Vaccines - pharmacokinetics

Animals

Vaccines, Subunit - pharmacology

Adjuvants, Immunologic - chemistry

Immunoglobulin G - immunology

Antibodies, Viral - immunology

Female

Spike Glycoprotein, Coronavirus - immunology

Mice

Mice, Inbred BALB C

Spike Glycoprotein, Coronavirus - pharmacology

Viral Vaccines - immunology

Details

Title: Subtitle: Identification of an ideal adjuvant for receptor-binding domain-based subunit vaccines against Middle East respiratory syndrome coronavirus
Creators: Naru Zhang - Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA
Rudragouda Channappanavar - Department of Microbiology, University of Iowa, Iowa City, IA, USA
Cuiqing Ma - Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA
Lili Wang - Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA
Jian Tang - Xiang-Ya Medical College, Central South University, Changsha, China
Tania Garron - Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA
Xinrong Tao - Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA
Sumaiya Tasneem - Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA
Lu Lu - Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai, Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China
Chien-Te K Tseng - Department of Microbiology and Immunology and Center for Biodefense and Emerging Disease, University of Texas Medical Branch, Galveston, TX, USA
Yusen Zhou - Xiang-Ya Medical College, Central South University, Changsha, China
Stanley Perlman - Department of Microbiology, University of Iowa, Iowa City, IA, USA
Shibo Jiang - Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai, Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China
Lanying Du - Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY, USA
Resource Type: Journal article
Publication Details: Cellular & molecular immunology, Vol.13(2), pp.180-190
DOI: 10.1038/cmi.2015.03
PMID: 25640653
PMCID: PMC4786625
NLM abbreviation: Cell Mol Immunol
ISSN: 1672-7681
eISSN: 2042-0226
Publisher: China
Grant note: R21AI109094 / NIAID NIH HHS R21 AI109094 / NIAID NIH HHS P01AI06099 / NIAID NIH HHS R01 AI091322 / NIAID NIH HHS P01 AI060699 / NIAID NIH HHS T32 AI060549 / NIAID NIH HHS
Language: English
Date published: 03/2016
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777468502771

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