Article abstract
Nature Medicine 14, 536 - 541 (2008)
Published online: 20 April 2008 | doi:10.1038/nm1757
Mast cell activators: a new class of highly effective vaccine adjuvants
James B McLachlan1,5, Christopher P Shelburne1,5, Justin P Hart1, Salvatore V Pizzo1, Rajen Goyal1, Rhea Brooking-Dixon1, Herman F Staats1,2,3 & Soman N Abraham1,2,4
Abstract
Mast cells (MCs) have recently received recognition as prominent effectors in the regulation of immune cell migration to draining lymph nodes and lymphocyte activation. However, their role in the development of humoral immune responses is not clear. Here, we demonstrate that subcutaneous or nasal administration of small-molecule MC activators with vaccine antigens evokes large increases in antigen-specific serum immunoglobulin G (IgG) responses. These responses were MC dependent and correlated with increased dendritic cell and lymphocyte recruitment to draining lymph nodes. Nasal instillation of these formulations also evoked antigen-specific secretory IgA and provided protection against anthrax lethal toxin challenge in vitro and against vaccinia virus infection in vivo. Collectively, these results define the MC as an integral sensory arm of the adaptive immune system. Moreover, they highlight MC activators as a new class of vaccine adjuvants, capable of inducing protective antigen-specific immune responses through needle-free routes of administration.
- Departments of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
- Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
- Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.
- Molecular Genetics & Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
- These authors contributed equally to this work.
Correspondence to: Soman N Abraham1,2,4 e-mail: soman.abraham@duke.edu
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