BCG Expressing LCR1 of Leishmania chagasi Induces Protective Immunity in Susceptible Mice

Judy A Streit; Thomas J Recker; John E Donelson; Mary E Wilson

doi:10.1006/expr.1999.4459

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BCG Expressing LCR1 of Leishmania chagasi Induces Protective Immunity in Susceptible Mice

Journal article

Peer reviewed

BCG Expressing LCR1 of Leishmania chagasi Induces Protective Immunity in Susceptible Mice

Judy A Streit, Thomas J Recker, John E Donelson and Mary E Wilson

Experimental parasitology, Vol.94(1), pp.33-41

01/2000

DOI: 10.1006/expr.1999.4459

PMID: 10631078

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Abstract

Streit, J. A., Recker, T. J., Donelson, J. E., and Wilson, M. E. 2000. BCG expressing LCR1 of Leishmania chagasi induces protective immunity in susceptible mice. Experimental Parasitology94, 33–41. Cellular immune responses are required for protective immunity against Leishmania chagasi. Immunization strategies using live intracellular bacteria (e.g., bacille-Calmette Guerin strain of Mycobacterium bovis) expressing recombinant antigens can induce cellular immune responses to these antigens. Previous studies demonstrated that the L. chagasi antigen LCR1 stimulates IFN-γ production from T cells of infected BALB/c mice, and immunization with recombinant LCR1 partially protects against L. chagasi infection. To determine whether live bacteria could enhance the immunization potential of LCR1, we engineered BCG expressing LCR1 (BCG–LCR1). Subcutaneous immunization with BCG–LCR1, but not with BCG containing plasmid only (BCG–pMV261), elicited better protective immunity against L. chagasi infection than LCR1 protein alone. BCG–LCR1 administered intraperitoneally did not protect. Splenocytes from mice immunized s.c. with either BCG–LCR1 or BCG–pMV261 and then infected with L. chagasi promastigotes had increased antigen-induced IFN-γ and reduced IL-10 production compared to splenocytes of control mice. We propose that BCG–LCR1 promotes a Th1-type protective immune response, and it may be a useful component of a Leishmania vaccine.

Th, CD4+ T cell helper

mAb, monoclonal antibody

RIBI, vaccine adjuvant

BCG, bacille-Calmette Guerin

Trypanosoma cruzi, protozoan cause of Chagas' disease

PBS, phosphate-buffered saline

CFU, colony-forming unit

IFN-γ, interferon-gamma

HBSS, Hanks' balanced salt solution

amastigote, intracellular form of Leishmania during mammalian infection

BSA, bovine serum albumin

i.v., intravenous

ELISA, enzyme-linked immunosorbant assay

GP63, glycoprotein 63, prominent surface protease of Leishmania

HOMEM, hemoflagellate minimal essential medium (culture medium)

BCG–pMV261 or BCG–LCR1, BCG transfected with plasmid pMV261, no insert, or BCG expressing recombinant protein LCR1, respectively

hsp, heat shock protein

promastigote, vector and cultural form of Leishmania

IgG, immunoglobulin G

i.p., intraperitoneal

LCR1, antigen cloned from amastigote L. chagasi library

IL, interleukin

s.c., subcutaneous

ConA, concanavalin A, a mitogen

Leishmania, an intracellular protozoan parasite

Leishmania chagasi and L. donovani, causes of visceral leishmaniasis

FCS, fetal calf serum

Details

Title: Subtitle: BCG Expressing LCR1 of Leishmania chagasi Induces Protective Immunity in Susceptible Mice
Creators: Judy A Streit - Department of Internal Medicine
Thomas J Recker - Department of Internal Medicine
John E Donelson - Department of Biochemistry, 300D EMRB
Mary E Wilson - Department of Internal Medicine
Resource Type: Journal article
Publication Details: Experimental parasitology, Vol.94(1), pp.33-41
Publisher: Elsevier Inc
DOI: 10.1006/expr.1999.4459
PMID: 10631078
ISSN: 0014-4894
eISSN: 1090-2449
Language: English
Date published: 01/2000
Academic Unit: Microbiology and Immunology; International Programs; Epidemiology; Biochemistry and Molecular Biology; Internal Medicine
Record Identifier: 9984001231002771

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