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Clin. Vaccine Immunol. doi:10.1128/CVI.00320-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Interleukin-15 Increases Vaccine Efficacy through a Mechanism Linked to Dendritic Cell Maturation and Enhanced Antibody Titers

Department of Immunology, Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702

^* To whom correspondence should be addressed. Email: Kamal_Saikh{at}Amedd.Army.Mil.

	Abstract

Interleukin-15 (IL-15) is generally considered to be a growth factor for natural killer cells and for sustaining T-cell memory. Previous data from our laboratory demonstrated that IL-15 is also an important factor for developing human dendritic cells. In this study, we investigated the effect of IL-15 on antibody responses in mice to a recombinant staphylococcal enterotoxin B (SEB) vaccine (STEBVax), in a pre-clinical model of toxic-shock syndrome induced by SEB. We observed that mouse spleen cells treated with IL-15 in ex vivo culture gained a dendritic cell-like phenotype. Administration of IL-15 to mice also resulted in an increased number of mature CD11c⁺ dendritic cells in mouse spleens. A significant, IL-15 dose-dependent increase in antigen-specific antibody was observed after co-administration with vaccine and an aluminum-based adjuvant (alhydrogel). Furthermore, the co-administration of IL-15 with STEBVax and alhydrogel also protected mice from lethal toxic shock above the levels that obtained without IL-15. Thus, the vaccine response enhanced by IL-15 appears to be mediated by mature dendritic cells, and results in prevalent sero-conversion to Th2-dependent antibodies. This suggests a potential use of IL-15 as an adjuvant for antibody-dependent responses to vaccines.