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Infection and Immunity, April 2002, p. 2022-2028, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.2022-2028.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Mucosal or Parenteral Administration of Microsphere-Associated Bacillus anthracis Protective Antigen Protects against Anthrax Infection in Mice

Helen C. Flick-Smith,1 Jim E. Eyles,1 Richard Hebdon,1 Emma L. Waters,1 Richard J. Beedham,1 Tony J. Stagg,1 Julie Miller,1 H. Oya Alpar,2 Les W. J. Baillie,1 and E. Diane Williamson1*

Dstl, Chemical and Biological Sciences, Porton Down, Salisbury, Wiltshire, SP4 0JQ,1 School of Pharmacy, University of London, Bloomsbury, London, WC1N 1AX, United Kingdom2

Received 30 July 2001/ Returned for modification 9 October 2001/ Accepted 30 November 2001

Existing licensed anthrax vaccines are administered parenterally and require multiple doses to induce protective immunity. This requires trained personnel and is not the optimum route for stimulating a mucosal immune response. Microencapsulation of vaccine antigens offers a number of advantages over traditional vaccine formulations, including stability without refrigeration and the potential for utilizing less invasive routes of administration. Recombinant protective antigen (rPA), the dominant antigen for protection against anthrax infection, was encapsulated in poly-L-lactide 100-kDa microspheres. Alternatively, rPA was loosely attached to the surfaces of microspheres by lyophilization. All of the microspheric formulations were administered to A/J mice with a two-dose schedule by either the intramuscular route, the intranasal route, or a combination of these two routes, and immunogenicity and protective efficacy were assessed. An intramuscular priming immunization followed by either an intramuscular or intranasal boost gave optimum anti-rPA immunoglobulin G titers. Despite differences in rPA-specific antibody titers, all immunized mice survived an injected challenge consisting of 103 median lethal doses of Bacillus anthracis STI spores. Immunization with microencapsulated and microsphere-associated formulations of rPA also protected against aerosol challenge with 30 median lethal doses of STI spores. These results show that rPA can be encapsulated and surface bound to polymeric microspheres without impairing its immunogenicity and also that mucosal or parenteral administration of microspheric formulations of rPA efficiently protects mice against both injected and aerosol challenges with B. anthracis spores. Microspheric formulations of rPA could represent the next generation of anthrax vaccines, which could require fewer doses because they are more potent, are less reactogenic than currently available human anthrax vaccines, and could be self-administered without injection.

* Corresponding author. Mailing address: Dstl, Chemical and Biological Sciences, Porton Down, Salisbury, Wiltshire SP4 0JQ, United Kingdom. Phone: 44-1980 614747. Fax: 44-1980 614307. E-mail: HCFSmith{at}dstl.gov.uk.

Editor: J. D. Clements

Infection and Immunity, April 2002, p. 2022-2028, Vol. 70, No. 4
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.4.2022-2028.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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