Abstract
Enterovirus 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.
Highlights
Enterovirus type 71 (EV71) is a small, nonenveloped, single-stranded RNA virus belonging to the human enterovirus A species of the family Picornaviridae[1,2,3]
EV71 infection in children is initiated through mucosal surfaces; mucosal immunisation could represent a promising method for protecting against EV71 infection in humans[23]
We demonstrated that CpG functioned as an effective mucosal adjuvant when administered IN with an EV71 vaccine in mice
Summary
Enterovirus type 71 (EV71) is a small, nonenveloped, single-stranded RNA virus belonging to the human enterovirus A species of the family Picornaviridae[1,2,3]. EV71 can potentially infect the central nervous system (CNS), and a vaccine that is effective against EV71 could prevent virus-induced morbidity and mortality. Our aim was to investigate a safe, needle-free EV71 vaccine for young children, a vaccine for mucosal delivery. Nasal inoculation with appropriate adjuvants is generating considerable research interest because this approach has the potential to establish robust mucosal immune responses while causing little pain or resistance compared with injections, in children and newborns[14]. Type C CpG ODNs potently induce IFN-α secretion from pDCs and strongly activate B cells[19,20]. Mucosal immunisation with inactivated EV71 in formulation with this CpG ODN (hereafter referred to as CpG) effectively induced broad-spectrum immune responses; this CpG-adjuvanted vaccine may represent a promising mucosal-vaccine candidate for preventing EV71 infection
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