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Heit, A.* ; Schmitz, F.* ; Haas, T.* ; Busch, D.H. ; Wagner, H.*

Antigen co-encapsulated with adjuvants efficiently drive protective T cell immunity.

Eur. J. Immunol. 37, 2063-2074 (2007)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Compared to "live" vaccines, the immunogenicity of "subunit" vaccines based on recombinant antigen (Ag) is poor, presumably because exogenous Ag fails to effectively access the endosomal Ag-processing pathways of Ag-presenting cells (APC). To overcome this limitation, we exploited biodegradable poly(lactic-co-glycolic) microspheres (MP) co-entrapping Ag and Toll-like receptor (TLR) 9 or 7 ligands as an endosomal delivery device. In vitro, microspheres were rapidly phagocytosed by APC and translocated into phago-endosomal compartments, followed by degradation of the Ag and concurrent activation of endosomal TLR. As a consequence, full maturation of and cytokine secretion by APC as well as Ag-cross-presentation ensued. In vivo, "loaded" microspheres triggered clonal expansion of primary and secondary Ag-specific CD4 and CD8 T cells. The efficacy of CD8 T cell cross-priming was comparable to that of live vectors. The potency of T cell vaccination was demonstrated by protective and therapeutic interventions using infection- and tumor-model systems. These preclinical "subunit" vaccination data thus recommend MP as a generally applicable and powerful endosomal delivery device of exogenous Ag plus TLR-based adjuvants to vaccinate for protective and therapeutic CD4 and CD8 T cell immunity.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Dendritic cells; T cells; Vaccination
ISSN (print) / ISBN 0014-2980
e-ISSN 1521-4141
Journal European Journal of Immunology
Quellenangaben Volume: 37, Issue: 8, Pages: 2063-2074 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)