title: Immunogenicity studies of bivalent inactivated virions of EV71/CVA16 formulated with submicron emulsion systems.
abstract: We assessed two strategies for preparing candidate vaccines against hand, foot, and mouth disease (HFMD) caused mainly by infections of enterovirus (EV) 71 and coxsackievirus (CV) A16. We firstly design and optimize the potency of adjuvant combinations of emulsion-based delivery systems, using EV71 candidate vaccine as a model. We then perform immunogenicity studies in mice of EV71/CVA16 antigen combinations formulated with PELC/CpG. A single dose of inactivated EV71 virion (0.2 μg) emulsified in submicron particles was found (i) to induce potent antigen-specific neutralizing antibody responses and (ii) consistently to elicit broad antibody responses against EV71 neutralization epitopes. A single dose immunogenicity study of bivalent activated EV71/CVA16 virion formulated with either Alum or PELC/CpG adjuvant showed that CVA16 antigen failed to elicit CVA16 neutralizing antibody responses and did not affect EV71-specific neutralizing antibody responses. A boosting dose of emulsified EV71/CVA16 bivalent vaccine candidate was found to be necessary to achieve high seroconversion of CVA16-specific neutralizing antibody responses. The current results are important for the design and development of prophylactic vaccines against HFMD and other emerging infectious diseases.
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan.
authors.forename: Chih-Wei
authors.initials: CW
authors.lastname: Lin
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan.
authors.forename: Chia-Chyi
authors.identifier: 0000-0002-6257-0389
authors.initials: CC
authors.lastname: Liu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan.
authors.forename: Tsung-Chun
authors.initials: TC
authors.lastname: Lu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan ; Graduate Institute of Immunology, China Medical University, Taichung 40402, Taiwan.
authors.forename: Shih-Jen
authors.identifier: 0000-0002-8736-1452
authors.initials: SJ
authors.lastname: Liu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan.
authors.forename: Yen-Hung
authors.initials: YH
authors.lastname: Chow
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan ; Graduate Institute of Immunology, China Medical University, Taichung 40402, Taiwan.
authors.forename: Pele
authors.identifier: 0000-0003-4197-7160
authors.initials: P
authors.lastname: Chong
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County 35053, Taiwan ; Biotechnology Center, National Chung Hsing University, Taichung 40227, Taiwan.
authors.forename: Ming-Hsi
authors.initials: MH
authors.lastname: Huang
mesh_terms: D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral / Q000276:immunology; D000956:Antigens, Viral / Q000276:immunology; D002522:Chlorocebus aethiops; D004655:Emulsions; D029821:Enterovirus A, Human / Q000276:immunology*; D004769:Enterovirus Infections / Q000276:immunology* / Q000517:prevention & control*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D009838:Oligodeoxyribonucleotides; D010316:Particle Size; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D014709:Vero Cells; D014765:Viral Vaccines / Q000276:immunology; D014771:Virion / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; C408982:CPG-oligonucleotide; D004655:Emulsions; D000939:Epitopes; D007074:Immunoglobulin G; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D014765:Viral Vaccines