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Infection and Immunity, August 2007, p. 4020-4029, Vol. 75, No. 8
0019-9567/07/$08.00+0     doi:10.1128/IAI.00070-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Mucosal Immunization with a Novel Nanoemulsion-Based Recombinant Anthrax Protective Antigen Vaccine Protects against Bacillus anthracis Spore Challenge{triangledown}

Anna U. Bielinska,1 Katarzyna W. Janczak,1 Jeffrey J. Landers,1 Paul Makidon,1 Laurie E. Sower,2 Johnny W. Peterson,2 and James R. Baker Jr.1*

Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, Ann Arbor, Michigan,1 Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas2

Received 12 January 2007/ Returned for modification 30 March 2007/ Accepted 1 May 2007

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 nontoxic, water-in-oil nanoemulsion (NE). This material does not contain a proinflammatory component but penetrates mucosal surfaces to load antigens into dendritic cells. Mice and guinea pigs were intranasally immunized with recombinant Bacillus anthracis protective antigen (rPA) mixed in NE as an adjuvant. rPA-NE immunization was effective in inducing both serum anti-PA immunoglobulin G (IgG) and bronchial anti-PA IgA and IgG antibodies after either one or two mucosal administrations. Serum anti-PA IgG2a and IgG2b antibodies and PA-specific cytokine induction after immunization indicate a Th1-polarized immune response. rPA-NE immunization also produced high titers of lethal-toxin-neutralizing serum antibodies in both mice and guinea pigs. Guinea pigs nasally immunized with rPA-NE vaccine were protected against an intradermal challenge with ~1,000 times the 50% lethal dose (~1,000x LD50) of B. anthracis Ames strain spores (1.38 x 103 spores), which killed control animals within 96 h. Nasal immunization also resulted in 70% and 40% survival rates against intranasal challenge with 10x LD50 and 100x 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.

* Corresponding author. Mailing address: Michigan Nanotechnology Institute for Medicine and Biological Sciences (MNIMBS), University of Michigan, 9220C MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0648. Phone: (734) 647-2777. Fax: (734) 936-2990. E-mail: jbakerjr{at}umich.edu

{triangledown} Published ahead of print on 14 May 2007.

Editor: J. N. Weiser

Infection and Immunity, August 2007, p. 4020-4029, Vol. 75, No. 8
0019-9567/07/$08.00+0     doi:10.1128/IAI.00070-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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