HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Bitsaktsis, C. Articles by Gosselin, E. J. Search for Related Content PubMed PubMed Citation Articles by Bitsaktsis, C. Articles by Gosselin, E. J.

Differential Requirements for Protection against Mucosal Challenge with Francisella tularensis in the Presence versus Absence of Cholera Toxin B and Inactivated F. tularensis ¹

Constantine Bitsaktsis^2,*, Deepak B. Rawool^2,, Ying Li^*, Nitin V. Kurkure, Bibiana Iglesias^* and Edmund J. Gosselin^3,*

^* Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208; Institute of Medical Microbiology, Genome Research, Justus-Liebig-University, Giessen, Germany; and Nagpur Veterinary College, Maharashtra Animal and Fishery Sciences University, Seminary Hills, Nagpur, India

Francisella tularensis is a category A biothreat agent for which there is no approved vaccine and the correlates of protection are not well understood. In particular, the relationship between the humoral and cellular immune response to F. tularensis and the relative importance of each in protection is controversial. Yet, understanding this relationship will be crucial to the development of an effective vaccine against this organism. We demonstrate, for the first time, a differential requirement for humoral vs cellular immunity in vaccine-induced protection against F. tularensis infection, and that the requirement for Ab observed in some protection studies, may be overcome through the induction of enhanced cellular immunity. Specifically, following intranasal/mucosal immunization of mice with inactivated F. tularensis organisms plus the cholera toxin B subunit, we observe increased production of IgG2a/2c vs IgG1 Ab, as well as IFN-, indicating induction of a Th1 response. In addition, the requirement for F. tularensis-specific IgA Ab production, observed in studies following immunization with inactivated F. tularensis alone, is eliminated. Thus, these data indicate that enhanced Th1 responses can supersede the requirement for anti-F. tularensis-specific IgA. This observation also has important ramifications for vaccine development against this organism.

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 grants from the National Institutes of Health (P01 AI056320 and R21 AI065476).

² C.B. and D.B.R. contributed equally to this manuscript.

³ 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: gosseline{at}mail.amc.edu

⁴ Abbreviations used in this paper: LVS, F. tularensis live vaccine strain; iFt, inactivated F. tularensis; OMP, outer membrane protein; i.n., intranasal(ly); CTB, cholera toxin B; BAL, bronchial alveolar lavage; CBA, cytometric bead array.