Intranasal Administration of Synthetic Recombinant Peptide-Based Vaccine Protects Mice from Infection bySchistosoma mansoni

Abstract

Schistosomiasis is the cause of a chronic debilitating disease which accounts for significant mortality and morbidity every year, especially in tropical and subtropical areas. An epitope derived from the protective surface protein 9B-Ag of Schistosoma mansoni, designated 9B peptide-1, was previously showed to be protective in mice when conjugated to bovine serum albumin and administered subcutaneously in complete Freund’s adjuvant. In this work, this protective peptide was expressed in the flagellin of aSalmonella vaccine strain, and the isolated recombinant flagella were used for immunization of mice. Since during the invasion of the parasite into the host the schistosomula migrate first to the lungs, the intranasal route of administration was employed in order to halt the parasite at an early stage of the infection. Such intranasal immunization with this peptide expressed in flagellin, without the addition of adjuvants, resulted in a significant humoral response and also led to protection against challenge infection, manifested as a reduction of the worm burden by an average of 42%.

Mucosal adjuvant activity of flagellin in aged mice

“…Previous work has shown that i.n. immunization of young mice with flagellin is highly effective at promoting protective immunity (McEwen et al, 1992;Levi and Arnon, 1996;Ben-Yedidia et al, 1999;Honko et al, 2006). To compare the innate response to i.n.…”

“…Its adjuvant activity is believed to result from its ability to promote dendritic cell maturation (McSorley et al, 2002;Means et al, 2003;Cuadros et al, 2004;Pino, 2005) and consequently facilitate antigen specific T cell proliferation (McSorley et al, 2002). Flagellin has also been shown to be an effective systemic and mucosal adjuvant in mice (McEwen et al, 1992;Levi and Arnon, 1996;Ben-Yedidia et al, 1999;Strindelius et al, 2004;Honko et al, 2006) and non-human primates (Honko et al, 2006). Additionally, intratracheal (i.t.)…”

“…Flagellin has been shown to be effective at promoting anti-viral immunity in aged mice (Ben-Yedidia et al, 1998). In view of flagellin's efficacy as an adjuvant for immunization against bacterial (Newton et al, 1989;Honko et al, 2006), viral (McEwen et al, 1992Levi and Arnon, 1996;Ben-Yedidia et al, 1998), and parasitic infections (Ben-Yedidia et al, 1999) in young mice, we have evaluated its ability to function as a Y. pestis vaccine adjuvant in aged mice.…”

A Recombinant Flagellin-Poxvirus Fusion Protein Vaccine Elicits Complement-Dependent Protection Against Respiratory Challenge with Vaccinia Virus in Mice

“…Work from our laboratory (3,4,24,39,42,43) as well as that of other investigators (5)(6)(7)(8)11,28,29,32,33,37,38) has established that flagellin, the major structural protein of gramnegative bacteria, is a potent adjuvant when administered with an antigen by any of several different routes. Flagellin binds to a leucine-rich repeat of toll-like receptor 5 (TLR5) (40), and induces downstream signaling in a MyD88dependent manner (21).…”

Therapeutic MUC1-Based Cancer Vaccine Expressed in Flagella-Efficacy in an Aggressive Model of Breast Cancer

“…The carrier system employed in this study has been designed to stimulate the immune response to linear epitopes by their expression in flagellin, the structural subunit of the flagellum filament [7]. In previous studies carried out in our laboratory, it was demonstrated that immunization with recombinant flagella expressing epitopes of various viral and bacterial pathogens evoked humoral as well as cellular immune responses against the inserted epitope, which resulted in protection against a challenge infection [8][9][10][11][12][13][14]. In these studies, the flagella, which is a known ligand of the Toll-like receptor 5 [15], acted as both carrier and adjuvant thus rendering superfluous the need for external adjuvant.…”