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Infection and Immunity, September 2009, p. 3909-3918, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00487-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Protection against Intestinal Amebiasis by a Recombinant Vaccine Is Transferable by T Cells and Mediated by Gamma Interferon{triangledown}

Xiaoti Guo,1,2 Lisa Barroso,3 Steven M. Becker,1 David M. Lyerly,3 Thomas S. Vedvick,4 Steven G. Reed,4 William A. Petri Jr.,1,2*,{dagger} and Eric R. Houpt1*,{dagger}

Division of Infectious Diseases and International Health, Department of Internal Medicine,1 Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908,2 TechLab Incorporated, Blacksburg, Virginia 24060,3 Infectious Disease Research Institute, Seattle, Washington 981044

Received 3 May 2009/ Returned for modification 16 June 2009/ Accepted 22 June 2009

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 demonstrated with adoptive-transfer experiments that this lectin vaccine protection is mediated by T cells but not serum. The cell-mediated immune (CMI) response was characterized by significant gamma interferon (IFN-{gamma}), interleukin 12 (IL-12), IL-2, IL-10, and IL-17 production. To move toward a human vaccine, we switched to a recombinant protein and tested a range of adjuvants and routes appropriate for humans. We found that subcutaneous delivery of LecA with IDRI's 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 to 68% of mice. Several antibody and CMI cytokine responses were examined for correlates of protection, and prechallenge IFN-{gamma}+ or IFN-{gamma}-, IL-2-, and tumor necrosis factor alpha-triple-positive CD4 cells in blood were statistically associated with protection. To test the role of IFN-{gamma} in LecA-mediated protection, we neutralized IFN-{gamma} in LecA-immunized mice and found that it abrogated the protection conferred by vaccination. These data demonstrate that CMI is sufficient for vaccine protection from intestinal amebiasis and reveal an important role for IFN-{gamma}, even in the setting of alum.

* Corresponding author. Mailing address: Division of Infectious Diseases and International Health, Department of Internal Medicine, University of Virginia, Charlottesville, VA 22908. Phone for Eric R. Houpt: (434) 243-9326. Fax: (434) 924-0075. E-mail: erh6k{at}virginia.edu. Phone for William A. Petri, Jr.: (434) 924-5621. Fax: (434) 924-0075. E-mail: wap3g{at}virginia.edu

{triangledown} Published ahead of print on 29 June 2009.

Editor: J. F. Urban, Jr.

{dagger} W.A.P. and E.R.H. contributed equally to this study.

Infection and Immunity, September 2009, p. 3909-3918, Vol. 77, No. 9
0019-9567/09/$08.00+0     doi:10.1128/IAI.00487-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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