IAI Accepts, published online ahead of print on 14 May 2007

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Infect. Immun. doi:10.1128/IAI.00070-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Mucosal Immunization with a Novel Nanoemulsion-based Recombinant Anthrax Protective Antigen Vaccine Protects against B. anthracis Spore Challenge

Anna U. Bielinska, Katarzyna W. Janczak, Jeffrey J. Landers, Paul Makidon, Laurie E. Sower, Johnny W. Peterson, and James R. Baker Jr.^*

MNIMBS, University of Michigan, Ann Arbor, MI, and Department of Microbiology & Immunology, University of Texas Medical Branch, Galveston, TX

^* To whom correspondence should be addressed. Email: jbakerjr{at}umich.edu.

The currently available commercial human anthrax vaccine requires multiple injections for efficacy and has side effects due to its alum adjuvant. These factors limit its utility when immunizing exposed populations in emergent situations. We evaluated a novel mucosal adjuvant that consists of a non-toxic, water-in-oil nanoemulsion (NE). This material does not contain a pro-inflammatory component, but penetrates mucosal surfaces to load antigens into dendritic cells. Mice and guinea pigs were intranasally immunized with recombinant B. anthracis Protective Antigen (rPA) mixed in NE as an adjuvant. rPA/NE immunization was effective in inducing both serum anti-PA IgG and bronchial anti-PA IgA and IgG antibodies after either one or two mucosal administrations. Serum anti-PA IgG_2a and IgG_2b antibodies and PA-specific cytokine induction after immunization indicate a Th1 polarized immune response. rPA/NE immunization also produced high titers of the Lethal Toxin neutralizing serum antibodies in both mice and guinea pigs. Guinea pigs nasally immunized with rPA/NE vaccine were protected against a 1000 x LD₅₀ (1.38 x 10³ spores) intradermal challenge of B. anthracis Ames strain spores that killed control animals within 96 hours. Nasal immunization also resulted in 70% and 40% survival rates against intranasal challenge with 10 x LD₅₀ and 100 x LD₅₀ (1.2 x 10⁶ and 1.2 x 10⁷) Ames strain spores. Our results indicate that NE can effectively adjuvant rPA for intranasal immunization. This potentially could lead to a needle-free anthrax vaccine requiring fewer doses and having fewer side effects than the currently available human vaccine.

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