Differential Requirements for Protection Against Mucosal Challenge with Francisella Tularensis in the Presence Versus Absence of Cholera Toxin B and Inactivated F. Tularensis

Overview

Journal J Immunol

Specialty Allergy & Immunology

Date 2009 Apr 4

PMID 19342669

Citations 23

Authors

Constantine Bitsaktsis

Deepak B Rawool

Ying Li

Nitin V Kurkure

Bibiana Iglesias

Edmund J Gosselin

Affiliations

Soon will be listed here.

Abstract

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-gamma, 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.

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