Interleukin-15 increases vaccine efficacy through a mechanism linked to dendritic cell maturation and enhanced antibody titers.
Interleukin-15 (IL-15) is generally considered to sustain T-cell memory and to be a growth factor for natural killer cells. Previous data from our laboratory demonstrated that IL-15 is also an important factor for developing human dendritic cells. For this study, we investigated the effects of IL-15 on antibody responses in mice to a recombinant staphylococcal enterotoxin B (SEB) vaccine (STEBVax) in a preclinical 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 coadministration with the vaccine and an aluminum-based adjuvant (alhydrogel). Furthermore, the coadministration 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 seroconversion to Th2-dependent antibodies. This suggests a potential use of IL-15 as an adjuvant for antibody-dependent responses to vaccines.
Saikh
Kamal U
KU
Department of Immunology, Army Medical Research Institute of Infectious Diseases, 1425 Porter Street, Frederick, MD 21702, USA. kamal.saikh@amedd.army.mil
Kissner
Teri L
TL
Nystrom
Steven
S
Ruthel
Gordon
G
Ulrich
Robert G
RG
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000536:Aluminum Hydroxide / Q000276:immunology / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D000917:Antibody Formation; D001428:Bacterial Vaccines / Q000276:immunology* / Q000627:therapeutic use; D039521:CD11c Antigen / Q000096:biosynthesis / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D004768:Enterotoxins / Q000276:immunology*; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012772:Shock, Septic / Q000276:immunology / Q000517:prevention & control; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D013211:Staphylococcus aureus / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D039521:CD11c Antigen; D004768:Enterotoxins; D007074:Immunoglobulin G; D019409:Interleukin-15; D019444:Vaccines, DNA; C031818:enterotoxin B, staphylococcal; D000536:Aluminum Hydroxide