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Infection and Immunity, August 2001, p. 4719-4725, Vol. 69, No. 8
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.8.4719-4725.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Leishmania donovani p36(LACK) DNA
Vaccine Is Highly Immunogenic but Not Protective against Experimental
Visceral Leishmaniasis
Peter C.
Melby,1,2,3,*
Jue
Yang,1
Weiguo
Zhao,1
Luis E.
Perez,1 and
Jun
Cheng1,
Medical Service, Department of Veterans
Affairs Medical Center, South Texas Veterans Health Care
System,1 and Departments of
Medicine2 and
Microbiology,3 University of Texas
Health Science Center, San Antonio, Texas
Received 10 January 2001/Returned for modification 22 February
2001/Accepted 1 May 2001
The acquisition of immunity following subclinical or resolved
infection with the intracellular parasite Leishmania
donovani suggests that vaccination could prevent visceral
leishmaniasis (VL). The LACK (Leishmania homolog of
receptors for activated C kinase) antigen is of interest as a vaccine
candidate for the leishmaniases because of its immunopathogenic role in
murine L. major infection. Immunization of mice with a
truncated (24-kDa) version of the 36-kDa LACK antigen, delivered in
either protein or DNA form, was found previously to protect against
cutaneous L. major infection by redirecting the early
T-cell response away from a pathogenic interleukin-4 (IL-4) response
and toward a protective Th1 response. The amino acid sequence of the
Leishmania p36(LACK) antigen is highly conserved, but the
efficacy of this vaccine antigen in preventing disease caused by
strains other than L. major has not been determined. We
investigated the efficacy of a p36(LACK) DNA vaccine against VL because
of the serious nature of this form of leishmaniasis and because it was
unclear whether the LACK vaccine would be effective in a model where
there was not a dominant pathogenic IL-4 response. We demonstrate here
that although the LACK DNA vaccine induced a robust parasite-specific Th1 immune response (IFN-
but not IL-4 production) and primed for an
in vivo T-cell response to inoculated parasites, it did not induce
protection against cutaneous or systemic L. donovani challenge. Coadministration of IL-12 DNA with the vaccine did not
enhance the strong vaccine-induced Th1 response or augment a protective effect.
*
Corresponding author. Mailing address: Department of
Medicine, Division of Infectious Diseases, University of Texas Health Science Center, 7703 Floyd Curl Dr., Mailcode 7881, San Antonio, TX
78229-3900. Phone: (210) 567-4614. Fax: (210) 567-4670. E-mail: melby{at}uthscsa.edu.

Present address: Gene Therapy Research Center, Institute of
infectious Diseases, The 302 Hospital of PLA, Beijing,
China.
Infection and Immunity, August 2001, p. 4719-4725, Vol. 69, No. 8
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.8.4719-4725.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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