title: Mucosal immunization with a novel nanoemulsion-based recombinant anthrax protective antigen vaccine protects against Bacillus anthracis spore challenge.
abstract: 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 approximately 1,000 times the 50% lethal dose ( approximately 1,000x LD(50)) of B. anthracis Ames strain spores (1.38 x 10(3) spores), which killed control animals within 96 h. Nasal immunization also resulted in 70% and 40% survival rates against intranasal challenge with 10x LD(50) and 100x LD(50) (1.2 x 10(6) and 1.2 x 10(7)) 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.
authors.affiliation: Michigan Nanotechnology Institute for Medicine and Biological Sciences, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0648, USA.
authors.forename: Anna U
authors.initials: AU
authors.lastname: Bielinska
authors.forename: Katarzyna W
authors.initials: KW
authors.lastname: Janczak
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Landers
authors.forename: Paul
authors.initials: P
authors.lastname: Makidon
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Sower
authors.forename: Johnny W
authors.initials: JW
authors.lastname: Peterson
authors.forename: James R
authors.initials: JR
authors.lastname: Baker
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000818:Animals; D000881:Anthrax / Q000517:prevention & control*; D022122:Anthrax Vaccines / Q000276:immunology*; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000276:immunology*; D000992:Antitoxins / Q000097:blood; D001408:Bacillus anthracis / Q000276:immunology; D001427:Bacterial Toxins / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004195:Disease Models, Animal; D004655:Emulsions; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D053758:Nanoparticles; D016019:Survival Analysis; D014611:Vaccination / Q000379:methods*; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D022122:Anthrax Vaccines; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000992:Antitoxins; D001427:Bacterial Toxins; D004655:Emulsions; D007074:Immunoglobulin G; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; C030325:anthrax toxin