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Infection and Immunity, December 2009, p. 5623-5630, Vol. 77, No. 12
0019-9567/09/$08.00+0     doi:10.1128/IAI.00508-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Vaccination with the ML0276 Antigen Reduces Local Inflammation but Not Bacterial Burden during Experimental Mycobacterium leprae Infection{triangledown}

Vanitha S. Raman,1 Joanne O'Donnell,1 H. Remy Bailor,1 Wakako Goto,1 Ramanuj Lahiri,2 Thomas P. Gillis,2 Steven G. Reed,1 and Malcolm S. Duthie1,3*

Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, Washington 98104,1 Laboratory Research Branch, National Hansen's Disease Programs, Baton Rouge, Louisiana,2 Protein AI, 1102 Columbia St., Seattle, Washington 981043

Received 6 May 2009/ Returned for modification 26 June 2009/ Accepted 18 September 2009

Leprosy elimination has been a goal of the WHO for the past 15 years. Widespread BCG vaccination and multidrug therapy have dramatically reduced worldwide leprosy prevalence, but new case detection rates have remained relatively constant. These data suggest that additional control strategies, such as a subunit vaccine, are required to block transmission and to improve leprosy control. We recently identified several Mycobacterium leprae antigens that stimulate gamma interferon (IFN-{gamma}) secretion upon incubation with blood from paucibacillary leprosy patients, a group who limit M. leprae growth and dissemination. In this study, we demonstrate that M. leprae-specific mouse T-cell lines recognize several of these antigens, with the ML0276 protein stimulating the most IFN-{gamma} secretion. We then examined if the ML0276 protein could be used in a subunit vaccine to provide protection against experimental M. leprae infection. Our data demonstrate that combining ML0276 with either a Toll-like receptor 4 (TLR4) (EM005), TLR7 (imiquimod), or TLR9 (CpG DNA) agonist during immunization induces Th1 responses that limit local inflammation upon experimental M. leprae infection. Our data indicate that only the ML0276/EM005 regimen is able to elicit a response that is transferable to recipient mice. Despite the potent Th1 response induced by this regimen, it could not provide protection in terms of limiting bacterial growth. We conclude that EM005 is the most potent adjuvant for stimulating a Th1 response and indicate that while a subunit vaccine containing the ML0276 protein may be useful for the prevention of immune pathology during leprosy, it will not control bacterial burden and is therefore unlikely to interrupt disease transmission.

* Corresponding author. Mailing address: Infectious Disease Research Institute, 1124 Columbia St., Suite 400, Seattle, WA 98104. Phone: (206) 330-2517. Fax: (206) 381-3678. E-mail: mduthie{at}idri.org

{triangledown} Published ahead of print on 28 September 2009.

Editor: J. L. Flynn

Infection and Immunity, December 2009, p. 5623-5630, Vol. 77, No. 12
0019-9567/09/$08.00+0     doi:10.1128/IAI.00508-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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