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Utilization of Fc Receptors as a Mucosal Vaccine Strategy against an Intracellular Bacterium, Francisella tularensis¹

Deepak B. Rawool^*, Constantine Bitsaktsis^*, Ying Li^*, Diane R. Gosselin^*, Yili Lin^*, Nitin V. Kurkure, Dennis W. Metzger^* and Edmund J. Gosselin^2,*

^* Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208; and Nagpur Veterinary College, Maharashtra Animal and Fishery Sciences University, Nagpur, India

Numerous studies have demonstrated that targeting Ag to Fc receptors (FcR) on APCs can enhance humoral and cellular immunity. However, studies are lacking that examine both the use of FcR-targeting in generating immune protection against infectious agents and the use of FcRs in the induction of mucosal immunity. Francisella tularensis is a category A intracellular mucosal pathogen. Thus, intense efforts are underway to develop a vaccine against this organism. We hypothesized that protection against mucosal infection with F. tularensis would be significantly enhanced by targeting inactivated F. tularensis live vaccine strain (iFt) to FcRs at mucosal sites, via intranasal immunization with mAb-iFt complexes. These studies demonstrate for the first time that: 1) FcR-targeted immunogen enhances immunogen-specific IgA production and protection against subsequent infection in an IgA-dependent manner, 2) FcR and neonatal FcR are crucial to this protection, and 3) inactivated F. tularensis, when targeted to FcRs, enhances protection against the highly virulent SchuS4 strain of F. tularensis, a category A biothreat agent. In summary, these studies show for the first time the use of FcRs as a highly effective vaccination strategy against a highly virulent mucosal intracellular pathogen.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ These studies were funded by a grant from the National Institutes of Health (P01 AI056320).

² Address correspondence and reprint requests to Dr. Edmund Gosselin, Center for Immunology and Microbial Disease, MC-151, Albany Medical College, 47 New Scotland Avenue, Albany, NY 12208. E-mail address: gossele{at}mail.amc.edu

³ Abbreviations used in this paper: FcR, Fc receptor; BAL, bronchoalveolar lavage; CBA, cytometric bead array; hFcRI, human FcRI; FcRn, neonatal FcR; iFt, inactivated F. tularensis live vaccine strain; i.n., intranasal; LVS, live vaccine strain; TT, tetanus toxoid.

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