Multiple CD4 and CD8 T-cell activation parameters predict vaccine efficacy in vivo mediated by individual DC-activating agonists

Marij J P Welters; Martijn S Bijker; Susan J F van den Eeden; Kees L M C Franken; Cornelis J M Melief; Rienk Offringa; Sjoerd H van der Burg

doi:10.1016/j.vaccine.2006.10.049

Multiple CD4 and CD8 T-cell activation parameters predict vaccine efficacy in vivo mediated by individual DC-activating agonists

Vaccine. 2007 Feb 9;25(8):1379-89. doi: 10.1016/j.vaccine.2006.10.049. Epub 2006 Nov 7.

Authors

Marij J P Welters¹, Martijn S Bijker, Susan J F van den Eeden, Kees L M C Franken, Cornelis J M Melief, Rienk Offringa, Sjoerd H van der Burg

Affiliation

¹ Departments of Immunohematology and Blood Transfusion, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.

PMID: 17123670
DOI: 10.1016/j.vaccine.2006.10.049

Abstract

A systematic comparison of the immunostimulatory capacity of TLR 2, 3, 4, 5, 7 and 9 agonists and an agonistic CD40-specific antibody was performed in a single long peptide vaccination model. All adjuvants activated DC in vitro but not all induced a strong functional T-cell response in vivo. Optimal clonal CD8(+) T-cell expansion depended on the capacity of agonists to mature pro-inflammatory DC and the duration of their in vivo stimulatory effect. Strong agonists promoted the induction of both antigen-specific IFNgamma-producing CD4(+) T-helper cells and high numbers of IFNgamma producing CD8(+) effector T-cells that killed target cells in vivo. Importantly, the capacity of an agonist to function as an adjuvant depended on the vaccine strategy used. Collectively, the multi-parameter system presented here can be used as a general road map to develop therapeutic vaccines.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic / pharmacology
Amino Acid Sequence
Animals
Antibodies / immunology
Antibodies / pharmacology
Antibody Specificity
CD4-Positive T-Lymphocytes / immunology*
CD40 Antigens / immunology
CD8-Positive T-Lymphocytes / immunology*
Cancer Vaccines / immunology*
Cell Line, Tumor
Dendritic Cells / immunology*
Female
Human papillomavirus 16 / immunology
Lymphocyte Activation
Mice
Mice, Inbred C57BL
Molecular Sequence Data
Neoplasms, Experimental / immunology*
Neoplasms, Experimental / therapy
Oncogene Proteins, Viral / immunology
Papillomavirus E7 Proteins
Toll-Like Receptors / agonists*
Toll-Like Receptors / immunology
Vaccines, Subunit / immunology*

Substances

Adjuvants, Immunologic
Antibodies
CD40 Antigens
Cancer Vaccines
Oncogene Proteins, Viral
Papillomavirus E7 Proteins
Toll-Like Receptors
Vaccines, Subunit
oncogene protein E7, Human papillomavirus type 16