IAI Accepts, published online ahead of print on 29 June 2009

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Infect. Immun. doi:10.1128/IAI.00487-09
Copyright (c) 2009, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Protection against Intestinal Amebiasis by a Recombinant Vaccine is Transferable by T cells and Mediated by IFN-

Xiaoti Guo, Lisa Barroso, Steven M. Becker, David M. Lyerly, Thomas S. Vedvick, Steven G. Reed, William A. Petri Jr.^*, and Eric R. Houpt^*

Division of Infectious Diseases and International Health, Department of Internal Medicine, Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908; TechLab Incorporated, Blacksburg, Virginia 24060; and Infectious Disease Research Institute, Seattle, Washington 98104

^* To whom correspondence should be addressed. Email: wap3g{at}virginia.edu. erh6k{at}virginia.edu.

We have previously shown that vaccination with purified Entamoeba histolytica Gal/GalNAc lectin or recombinant subunits can protect mice from intestinal amebiasis upon intracecal challenge. In this study, we demonstrate with adoptive transfer experiments that this lectin vaccine protection is mediated by T cells but not serum. The CMI response was characterized by significant IFN-, IL-12, IL-2, IL-10, and IL-17 production. To move towards a human vaccine, we switched to a recombinant protein and tested a range of human-appropriate adjuvants and routes. We found that subcutaneous delivery of LecA with IDRI adjuvant system EM014 elicited a potent Th1-type CMI profile and provided significant protection as measured by culture negativity (79% efficacy); intranasal immunization with Cholera toxin provided 56% efficacy; and alum induced a Th2-type response that protected 62-68% of mice. Several antibody and CMI cytokine responses were examined for correlates of protection and pre-challenge IFN-⁺ or IFN-, IL-2 and TNF--triple positive CD4 cells in blood were statistically associated with protection. To test the role of IFN- in LecA-mediated protection, we neutralized IFN- in LecA-immunized mice and found that it abrogated the protection conferred by vaccination. These data demonstrate that cell-mediated immunity is sufficient for vaccine protection from intestinal amebiasis, and reveal an important role for IFN-, even in the setting of alum.