NDLI: Complement activation and complement receptors on follicular dendritic cells are critical for the function of a targeted adjuvant.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Karlsson, Mikael C. I. Yrlid, Ulf Schön, Karin Lycke, Nils Y. Ravetch, Jeffrey V. Mattsson, Johan Stensson, Anneli
Description	Country affiliation: Sweden Author Affiliation: Mattsson J ( Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Center, Institute of Biomedicine, University of Gothenburg, 405 30 Gothenburg, Sweden.)
Abstract	A detailed understanding of how activation of innate immunity can be exploited to generate more effective vaccines is critically required. However, little is known about how to target adjuvants to generate safer and better vaccines. In this study, we describe an adjuvant that, through complement activation and binding to follicular dendritic cells (FDC), dramatically enhances germinal center (GC) formation, which results in greatly augmented Ab responses. The nontoxic CTA1-DD adjuvant hosts the ADP-ribosylating CTA1 subunit from cholera toxin and a dimer of the D fragment from Staphylococcus aureus protein A. We found that T cell-dependent, but not -independent, responses were augmented by CTA1-DD. GC reactions and serum Ab titers were both enhanced in a dose-dependent manner. This effect required complement activation, a property of the DD moiety. Deposition of CTA1-DD to the FDC network appeared to occur via the conduit system and was dependent on complement receptors on the FDC. Hence, Cr2(-/-) mice failed to augment GC reactions and exhibited dramatically reduced Ab responses, whereas Ribi adjuvant demonstrated unperturbed adjuvant function in these mice. Noteworthy, the adjuvant effect on priming of specific CD4 T cells was found to be intact in Cr2(-/-) mice, demonstrating that the CTA1-DD host both complement-dependent and -independent adjuvant properties. This is the first demonstration, to our knowledge, of an adjuvant that directly activates complement, enabling binding of the adjuvant to the FDC, which subsequently strongly promoted the GC reaction, leading to augmented serum Ab titers and long-term memory development.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	7
Volume Number	187
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2011-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Adjuvants, Immunologic Pharmacology Cholera Toxin Immunology Complement Activation Dendritic Cells, Follicular Receptors, Complement 3d Recombinant Fusion Proteins Chemical Synthesis Animals Cell Separation Metabolism Enzyme-linked Immunosorbent Assay Flow Cytometry Fluorescent Antibody Technique Germinal Center Mice Mice, Inbred Balb C Mice, Inbred C57bl Mice, Knockout Receptors, Complement Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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