title: Immunological and biochemical characterizations of coxsackievirus A6 and A10 viral particles.
abstract: Childhood exanthema caused by different serotypes of coxsackievirus (CV-A) and enterovirus A71 (EV-A71) has become a serious global health problem; it is commonly known as hand, foot, and mouth disease (HFMD). Current EV-A71 vaccine clinical trials have demonstrated that human antibody responses generated by EV-A71 vaccinations do not cross-neutralize coxsackievirus A16 (CV-A16). An effective multivalent HFMD vaccine is urgently needed. From molecular epidemiological studies in Southeast Asia, CV-A6 and CV-A10 are commonly found in HFMD outbreaks. In this study, CV-A6 and CV-A10 were individually cultured in rhabdomyosarcoma (RD) cells grown in medium containing serum, harvested and concentrated. In viral downstream purification, two viral fractions were separated by sucrose gradient zonal ultracentrifugation and detected using a SDS-PAGE analysis and a virus infectivity assay. These two viral fractions were formalin-inactivated, and only the infectious particle fraction was found to be capable of inducing CV-A serotype-specific neutralizing antibody responses in animal immunogenicity studies. These mouse and rabbit antisera also failed to cross-neutralize EV-A71 and CV-A16 infections. Only a combination of formalin-inactivated EV-A71, CV-A6, CV-A10 and CV-A16 multivalent vaccine candidates elicited cross-neutralizing antibody responses in both mouse and rabbit immunogenicity studies. The current results certainly provide important information for multivalent HFMD vaccine development.
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan. Electronic address: 010113@nhri.org.tw.
authors.forename: Chia-Chyi
authors.initials: CC
authors.lastname: Liu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan.
authors.forename: Meng-Shin
authors.initials: MS
authors.lastname: Guo
authors.affiliation: Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Shang-Rung
authors.initials: SR
authors.lastname: Wu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan.
authors.forename: Hsiao-Yu
authors.initials: HY
authors.lastname: Lin
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan.
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Yang
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan.
authors.forename: Wei-Chih
authors.initials: WC
authors.lastname: Liu
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors.forename: Yen-Hung
authors.initials: YH
authors.lastname: Chow
authors.affiliation: Institute of Oral Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Dar-Bin
authors.initials: DB
authors.lastname: Shieh
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan; Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Jen-Ren
authors.initials: JR
authors.lastname: Wang
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Zhunan Town, Miaoli County, Taiwan; Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.
authors.forename: Pele
authors.initials: P
authors.lastname: Chong
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000096:biosynthesis / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood / Q000276:immunology*; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology; D003429:Cross Reactions; D029821:Enterovirus A, Human / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification / Q000648:ultrastructure; D004769:Enterovirus Infections / Q000276:immunology; D005838:Genotype; D006232:Hand, Foot and Mouth Disease / Q000276:immunology / Q000821:virology; D051379:Mice; D011817:Rabbits; D016415:Sequence Alignment; D014611:Vaccination; D015164:Vaccines, Inactivated / Q000276:immunology; D056189:Viral Tropism; D014765:Viral Vaccines / Q000276:immunology*; D014771:Virion / Q000737:chemistry / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines
keywords: Coxsackievirus A10 (CV-A10); Coxsackievirus A6 (CV-A6); Hand, foot, and mouth diseases (HFMD); Inactivated whole-virion vaccine; Multivalent vaccine