CD8+ T cell adjuvant effects of Salmonella FliCd flagellin in live vaccine vectors or as purified protein

Department of Microbiology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes, 1374, São Paulo, SP 05008-000, Brazil.
Vaccine (Impact Factor: 3.49). 11/2009; 28(5):1373-82. DOI: 10.1016/j.vaccine.2009.11.003
Source: PubMed

ABSTRACT Salmonella flagellin, the flagellum structural subunit, has received particular interest as a vaccine adjuvant conferring enhanced immunogenity to soluble proteins or peptides, both for activation of antibody and cellular immune responses. In the present study, we evaluated the Salmonella enterica FliCd flagellin as a T cell vaccine adjuvant using as model the 9-mer (SYVPSAEQI) synthetic H2(d)-restricted CD8(+) T cell-specific epitope (CS(280-288)) derived from the Plasmodium yoelii circumsporozoite (CS) protein. The FliCd adjuvant effects were determined under two different conditions: (i) as recombinant flagella, expressed by orally delivered live S. Dublin vaccine strains expressing the target CS(280-288) peptide fused at the central hypervariable domain, and (ii) as purified protein in acellular vaccines in which flagellin was administered to mice either as a recombinant protein fused or admixed with the target CS(280-288) peptide. The results showed that CS(280-288)-specific cytotoxic CD8(+) T cells were primed when BALB/c mice were orally inoculated with the expressing the CS(280-288) epitope S. Dublin vaccine strain. In contrast, mice immunized with purified FliCd admixed with the CS(280-288) peptide and, to a lesser extent, fused with the target peptide developed specific cytotoxic CD8(+) T cell responses without the need of a heterologous booster immunization. The CD8(+) T cell adjuvant effects of flagellin, either fused or not with the target peptide, correlated with the in vivo activation of CD11c(+) dendritic cells. Taken together, the present results demonstrate that Salmonella flagellins are flexible adjuvant and induce adaptative immune responses when administered by different routes or vaccine formulations.

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Available from: Mauricio Rodrigues, Nov 24, 2014
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    • "In mammals, this interaction triggers a signaling cascade that results in expression of costimulatory molecules and production of cytokines by cells like macrophages and dendritic cells, leading to a more efficient activation of adaptive immune responses (Didierlaurent, 2004). Indeed, Salmonella flagellin, both as native or recombinant protein, has been intensively studied as an adjuvant in different vaccine formulations via parenteral or mucosal routes, either admixed or genetically fused to the target protein antigen (Gerwitz et al., 2001a; Gerwitz et al., 2001b; Hayashi et al., 2001; Moors et al., 2001; Liaudet et al., 2002; Huleatt et al., 2007; Uematsu et al., 2008; Bargieri et al., 2008; Bargieri et al., 2010; Braga et al., 2010;). Salmonella flagellin has been successfully tested as a cell protector, both in vitro and in vivo, against the toxic effects of chemical and radiological procedures commonly used in the treatment of cancer (Ramos et al., 2004; Vijay-Kumar et al., 2008; Sanders et al., 2008; Wang et al., 2008). "
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