title: The mast cell activator compound 48/80 is safe and effective when used as an adjuvant for intradermal immunization with Bacillus anthracis protective antigen.
abstract: We evaluated the safety and efficacy of the mast cell activator compound 48/80 (C48/80) when used as an adjuvant delivered intradermally (ID) with recombinant anthrax protective antigen (rPA) in comparison with two well-known adjuvants. Mice were vaccinated in the ear pinnae with rPA or rPA+C48/80, CpG oligodeoxynucleotides (CpG), or cholera toxin (CT). All adjuvants induced similar increases in serum anti-rPA IgG and lethal toxin neutralizing antibodies. C48/80 induced a balanced cytokine production (Th1/Th2/Th17) by antigen-restimulated splenocytes, minimal injection site inflammation, and no antigen-specific IgE. Histological analysis demonstrated that vaccination with C48/80 reduced the number of resident mast cells and induced an injection site neutrophil influx within 24h. Our data demonstrate that C48/80 is a safe and effective adjuvant, when used by the intradermal route, to induce protective antibody and balanced Th1/Th2/Th17 responses.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Afton L
authors.initials: AL
authors.lastname: McGowen
authors.forename: Laura P
authors.initials: LP
authors.lastname: Hale
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Shelburne
authors.forename: Soman N
authors.initials: SN
authors.lastname: Abraham
authors.forename: Herman F
authors.initials: HF
authors.lastname: Staats
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000279:Administration, Cutaneous; D000818:Animals; D022122:Anthrax Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D000942:Antigens, Bacterial / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D007114:Immunization; D007073:Immunoglobulin E / Q000096:biosynthesis; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008809:Mice, Inbred C3H; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D016207:Cytokines; C030325:anthrax toxin; D007073:Immunoglobulin E; D003189:p-Methoxy-N-methylphenethylamine