Mast cell activators: a new class of highly effective vaccine adjuvants.
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.
McLachlan
James B
JB
Department of Pathology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Shelburne
Christopher P
CP
Hart
Justin P
JP
Pizzo
Salvatore V
SV
Goyal
Rajen
R
Brooking-Dixon
Rhea
R
Staats
Herman F
HF
Abraham
Soman N
SN
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000917:Antibody Formation / Q000187:drug effects / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology; D053379:Chromogranin A / Q000276:immunology / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D007074:Immunoglobulin G / Q000276:immunology; D008221:Lymphoid Tissue / Q000187:drug effects* / Q000276:immunology; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D010455:Peptides / Q000276:immunology / Q000494:pharmacology; D014615:Vaccinia / Q000276:immunology; D003189:p-Methoxy-N-methylphenethylamine / Q000276:immunology / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D053379:Chromogranin A; D007074:Immunoglobulin G; D010446:Peptide Fragments; D010455:Peptides; C030325:anthrax toxin; C109084:chromogranin A (344-364); C008331:mast cell degranulating peptide; D003189:p-Methoxy-N-methylphenethylamine