Targeting split vaccines to the endosome improves vaccination.
Compared to 'live' vaccines, the immunogenicity of 'split' vaccines based on recombinant antigen (Ag) is poor, presumably because exogeneous recombinant Ag fails to efficiently access the major histocompatibility complex (MHC) class I processing pathway needed for 'cross-presentation'. Here we discuss recent evidence that targeting ligands of the Toll-like receptor 9 together with proteinaceous Ag to the endosome of dendritic cells conveys immunogenicity to Ag similar in magnitude to 'live' vaccines that produce Ag. Enforced endocytosis of Ag together with the adjuvant effect of Toll-like receptor 9 ligands might be key for the efficient cross-presentation of exogeneous Ag as well as for effective cross-priming of MHC class I restricted CD8 T effector cells.
Wagner
Hermann
H
Institute of Medical Microbiology, Immunology and Hygiene, Trogerstrasse. 9, 81675 Munich, Germany. h.wagner@lrz.tu-muenchen.de
Heit
Antje
A
Schmitz
Frank
F
Bauer
Stefan
S
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D045142:Cross-Priming / Q000276:immunology; D011992:Endosomes / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008024:Ligands; D008562:Membrane Glycoproteins / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011956:Receptors, Cell Surface / Q000276:immunology; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D014612:Vaccines / Q000276:immunology / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D008562:Membrane Glycoproteins; D011948:Receptors, Antigen, T-Cell; D011956:Receptors, Cell Surface; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors; D014612:Vaccines