Induction of CD8+T cell responses byYersiniavaccine carrier strains

• Published in: Vaccine 2005-10, Vol.23 (42), p.4984
• Main Authors: Wiedig, Carolin A, Kramer, Uwe, Garbom, Sara, Wolf-Watz, Hans, Autenrieth, Ingo B
• Format: Article
• Language: English
• Subjects: Genes; Immune system; Immunization; Plasmids; Rodents; T cell receptors; Translocation; Vaccines
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2005.05.027

Yersinia enterocoliticaemploys a type III secretion system (TTSS) to target virulence factors (e.g. YopE) into the cytosol of the host cells. We utilized the TTSS to introduce a recombinant antigen directly into the cytosol of host cells and to investigate the potential ofY. enterocoliticaandY. pseudotuberculosisas live carrier for vaccines. The model antigen ovalbumin (Ova) was fused to defined secretion or translocation domains of theYersiniaeffector protein YopE and introduced into attenuated mutant strains ofY. enterocoliticaandY. pseudotuberculosis. In vitro experiments showed secretion and translocation of YopE-Ova hybrid proteins into host cells. To investigate the resulting immune responses, mice expressing transgenic Ova-specific T cell receptors were used. BothY. enterocoliticaandY. pseudotuberculosismutants induced efficaciously Ova-specific CD8+T cell responses. The translocation domain of YopE was required for induction of CD8+T cell responses in vivo, but not for T cell responses induced in vitro. The in vivo frequency of Ova-specific splenic T cells was up to six-fold higher in mice immunized with YopE-Ova-translocatingY. enterocolitica/Y. pseudotuberculosismutants than in control mice. The Ova-specific T cells were shown to produce high amounts of IFN-gamma. We did not observe significant Ova-specific CD4+T cell or antibody responses upon vaccination with either of the strains. In conclusion,Yersinialive carrier vaccine strains are suitable to target antigens into the MHC class I pathway and stimulate CD8+T cell responses and thus, might be useful in vaccine approaches against intracellular pathogens.