Lin Y.-L.Chow Y.-H.LI-MIN HUANGSZU-MIN HSIEHCheng P.-Y.Hu K.-C.BOR-LUEN CHIANG2020-12-292020-12-2920182045-2322https://www.scopus.com/inward/record.uri?eid=2-s2.0-85050368210&doi=10.1038%2fs41598-018-28281-5&partnerID=40&md5=df92b5f9718514107b902374f479c04bhttps://scholars.lib.ntu.edu.tw/handle/123456789/535560Enterovirus 71 (EV71) is an aetiological agent responsible for seasonal epidemics of hand-foot-and-mouth disease, which causes considerable mortality among young children. Mucosal vaccines can efficiently induce secretory IgA at mucosal surfaces and thereby prevent or limit infection at the site of virus entry. CpG oligodeoxynucleotides (ODNs), which resemble bacterial DNA, can induce the innate immune response through activation of Toll-like receptor 9. Here, we used CpG ODNs as adjuvants to investigate an EV71 mucosal vaccine in mice. In the EV71 + CpG group, the EV71-specific IgG and IgA titres in the serum, nasal wash, bronchoalveolar lavage fluid, and faeces were substantially higher than those in the EV71- and phosphate-buffered saline-treated groups. Moreover, the number of EV71-specific IgG- and IgA-producing cells was also higher in the EV71 + CpG group. Furthermore, T-cell proliferative responses and interleukin-17 secretion were markedly increased when CpG-adjuvanted EV71 was delivered intranasally. More importantly, the induced antibodies neutralised infection by EV71 of the C2 genotype and crossneutralised infection by EV71 of the B4 and B5 genotypes. Lastly, human scavenger receptor class B, member 2-transgenic mice intranasally immunised with the CpG-adjuvanted EV71 vaccine resisted a subsequent lethal challenge with EV71, indicating that CpG was an effective intranasal adjuvant for EV71 mucosal-vaccine development. ? 2018 The Author(s).[SDGs]SDG3CPG-oligonucleotide; immunological adjuvant; inactivated vaccine; lysosome associated membrane protein; oligodeoxyribonucleotide; SCARB2 protein, human; scavenger receptor; virus antibody; virus vaccine; animal; Bagg albino mouse; blood; bronchoalveolar lavage fluid; disease model; Enterovirus A; female; genetics; hand foot and mouth disease; human; immunology; intranasal drug administration; mouse; mucosal immunity; pathogenicity; transgenic mouse; treatment outcome; vaccine immunogenicity; virology; Adjuvants, Immunologic; Administration, Intranasal; Animals; Antibodies, Viral; Bronchoalveolar Lavage Fluid; Disease Models, Animal; Enterovirus A, Human; Female; Hand, Foot and Mouth Disease; Humans; Immunity, Mucosal; Immunogenicity, Vaccine; Lysosome-Associated Membrane Glycoproteins; Mice; Mice, Inbred BALB C; Mice, Transgenic; Oligodeoxyribonucleotides; Receptors, Scavenger; Treatment Outcome; Vaccines, Inactivated; Viral Vaccinesjournal article10.1038/s41598-018-28281-530013088