Fibroblast-stimulating lipopeptide-1 as a potential mucosal adjuvant enhances mucosal and systemic immune responses to enterovirus 71 vaccine. Issue 29 (5th July 2018)

• Record Type: Journal Article
• Authors: Lin, Yu-Li; Cheng, Pei-Yun; Chin, Chiao-Li; Huang, Li-Min; Lin, Shr-Yu; Chiang, Bor-Luen
• Is Part Of: Vaccine. Volume 36:Issue 29(2018)
• Page Start: 4331
• Page End: 4338
• Publication Date: 2018-07-05
• Subjects: Adjuvant -- Enterovirus 71 -- FSL-1 -- IgA -- Mucosal vaccine -- Pam3CSK4; ASC antibody-secreting cell -- APC antigen-presenting cell -- Con A concanavalin A -- EV71 enterovirus 71 -- FBS fetal bovine serum -- FSL-1 fibroblast-stimulating lipopeptide-1 -- HFMD hand-foot-mouth disease -- HRP horseradish peroxidase -- IFN interferon -- IL interleukin -- LPS lipopolysaccharide -- PBS phosphate-buffered saline -- RD rhabdomyosarcoma -- RPMI Roswell Park Memorial Institute -- Th T helper -- TLR Toll-like receptor -- TMB 3, 3′, 5, 5′-tetramethylbenzidine; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2018.05.090
• Languages: English
• ISSNs: 0264-410X

Abstract

Abstract: To prevent viral infection at the site of entry, mucosal vaccines are potent tools for inducing IgA secretion for defense. Because Toll-like receptor (TLR) ligands serve as strong adjuvants, two ligands that mimic the structure of mycoplasmal and bacterial lipopeptides represent interesting vaccine candidates. Pam3CSK4, a synthetic triacylated lipopeptide, interacts with TLR2/1. Because fibroblast-stimulating lipopeptide-1 (FSL-1), a synthetic diacylated lipopeptide, is recognized by TLR2/6, we targeted the potential immuno-inducibility of Pam3CSK4 and FSL-1 as adjuvants of an enterovirus 71 (EV71) mucosal vaccine. Naïve BALB/c mice were used for intranasal immunization three times over a 3-week interval, with results showing that EV71-specific IgG and IgA in serum, nasal washes, bronchoalveolar lavage fluid, and feces from the EV71 + FSL-1 group were significantly higher than levels observed in mice treated with EV71 + Pam3CSK4, EV71 alone, or the control group treated with phosphate-buffered saline. Furthermore, we observed more EV71-specific IgG and IgA-producing cells in treatments using EV71 formulated with FSL-1. Additionally, T cell-proliferative responses and interferon-γ and interleukin-17 secretion were significantly increased when inactivated EV71 was formulated using FSL-1. Moreover, serum from immunized mice was capable of neutralizing the infectivity of EV71 (C2 genotype) and was able to cross-neutralize the B4 and B5 genotypes of EV71. Our data suggested that FSL-1 could be used as an efficient adjuvant for intranasal EV71-vaccine immunization.