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 24 hours. 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. KeywordsCompound 48/80; adjuvant safety; intradermal vaccination IntroductionImmunization programs have led to the eradication of smallpox, the near eradication of polio, and the control of other infectious diseases, including measles, mumps, rubella, and diphtheria. While there are many success stories, HIV, pandemic Influenza, and a variety of emerging Corresponding author: Herman F. Staats, Ph.D., Department of Pathology, Box 3712, DUMC, Durham, NC 27710, Telephone: 919-684-8823, herman.staats@duke.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptVaccine. Author manuscript; available in PMC 2010 June 2. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript infectious diseases (West Nile Virus, Dengue, etc.) provide active reminders that safe and effective vaccines continue to be needed to combat infectious diseases.Adjuvants are substances that, when combined with vaccine antigens, enhance the induction of the desired immune responses [1,2]. For example, the addition of adjuvants to vaccines may increase vaccine potency by enhancing the magnitude of antibody or cellular responses induced, reducing the time to seroprotection or selectively inducing CD4+ Th1, Th2, Th17, or CD8+ T cell responses [1,2]. The mechanism of action of adjuvants varies depending on the adjuvant used, but the end result is thought to include the activation and migration of dendritic cells as well as the expression of antigen presenting molecules, providing superior induction of antigen-specific T and B cell responses [1,2]. Despite increasing information on the mechanism of action ...

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