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

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

Author Braga, Catarina J. M. Google Scholar
Massis, Liliana M. Google Scholar
Sbrogio-Almeida, Maria E. Google Scholar
Alencar, Bruna C. G. Autor UNIFESP Google Scholar
Bargieri, Daniel Y. Autor UNIFESP Google Scholar
Boscardin, Silvia B. Google Scholar
Rodrigues, Mauricio M. Autor UNIFESP Google Scholar
Ferreira, Luis C. S. Google Scholar
Institution Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Butantan Inst
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 (CS280-288) derived from the Plasmodium yoelii circumsporozoite (G) 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 CS280-288 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 CS280-288 peptide. the results showed that CS280-288-specific cytotoxic CD8(+) T cells were primed when BALB/c mice were orally inoculated with the expressing the CS280-288 epitope S. Dublin vaccine strain. in contrast, mice immunized with purified FliCd admixed with the CS280-288 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. (C) 2009 Elsevier B.V. All rights reserved.
Keywords Flagellin
Adjuvants
T cell vaccines
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Millennium Institute for Vaccine Development and Technology
LCSF
LLM
MMR
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2010-02-03
Published in Vaccine. Oxford: Elsevier B.V., v. 28, n. 5, p. 1373-1382, 2010.
ISSN 0264-410X (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 1373-1382
Origin http://dx.doi.org/10.1016/j.vaccine.2009.11.003
Access rights Closed access
Type Article
Web of Science ID WOS:000275122200033
URI http://repositorio.unifesp.br/handle/11600/32261

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