Induction of a cellular immune response to a defined T-cell epitope as an insert in the flagellin of a live vaccine strain of Salmonella

Vaccine
N K VermaG K Schoolnik

Abstract

Attenuated strains of Salmonella have been used as vaccines to deliver heterologous antigens mainly to generate a humoral immune response. However, little is known about their ability to induce a cell-mediated immune response to the T-cell epitopes of another infectious agent or how optimally to deliver these epitopes to the host immune system. In order to study this question, a well defined MHC class II-restricted epitope (residues 88-103) from moth cytochrome C (MCC) was inserted into the central hypervariable domain of the flagellin of an attenuated strain of Salmonella dublin. The resulting flagellin was exported to the bacterial surface and polymerized into flagellar filaments that contained multiple copies of the MCC epitope. When flanked by Lys-Lys cathepsin B cleavage sites to facilitate its proteolytic release within the endosomal compartment of antigen-presenting cells, the MCC-chimeric flagellin epitope was efficiently processed in vitro by mouse peritoneal macrophages and presented to 2B4 T-hybridoma cells (specific for the MCC epitope 88-103). Stable expression of the epitope and a higher immune response was obtained in H-2k mice by integrating the chimeric flagellin gene into the chromosome of the vaccine strain. ...Continue Reading

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Citations

Apr 23, 2004·Infection and Immunity·Camilo CuadrosJoseph Lustgarten
Nov 2, 2004·BMC Biotechnology·Stefano PorzioAldo Tagliabue
Jul 16, 2014·Developmental and Comparative Immunology·Jana MonteroVictoriano Mulero
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Mar 13, 2001·The Veterinary Journal·P MastroeniG Dougan
Nov 12, 2010·BMC Genomics·Guillaume PosticKarin L Meibom
Jun 20, 2008·FEMS Microbiology Letters·Katalin KissEric J Hansen
Jun 27, 2013·Wiley Interdisciplinary Reviews. Developmental Biology·James D McGhee
May 20, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lucia SfondriniAndrea Balsari

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