Nonviable Burkholderia mallei Induces a Mixed Th1- and Th2-Like Cytokine Response in BALB/c Mice

Author:

Amemiya Kei1,Bush Gary V.1,DeShazer David1,Waag David M.1

Affiliation:

1. Pathogenesis and Immunology Branch, Bacteriology Division, United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, Maryland 21702

Abstract

ABSTRACT Nonviable cell preparations of Burkholderia mallei , the causative agent of glanders, were evaluated as potential vaccine candidates in a BALB/c murine model. Three different B. mallei cell preparations plus Alhydrogel were evaluated: a heat-killed preparation, an irradiation-inactivated preparation, and a preparation of a capsule-negative mutant strain which had been irradiation inactivated. BALB/c mice were vaccinated twice with the different B. mallei preparations, and spleens and sera were collected to determine their cellular and humoral immune responses. All three bacterial cell preparations had essentially the same results in two cellular immune response assays. In a splenocyte proliferation assay, the amount of cell proliferation in response to the homologous immunogen, concanavalin A, or lipopolysaccharide was similar for all the cell preparations. Also, splenocytes from the inoculated mice expressed interleukin 2 (IL-2), gamma interferon, and small amounts of IL-4 and IL-5, and more IL-10 cytokine in the presence of the homologous antigen. When the immunoglobulin subclasses from these mice were examined, they all produced higher levels of IgG1 than IgG2a subclasses. The higher ratio of IgG1 to IgG2a was not due to the amount of the immunogen or the adjuvant (Alhydrogel) used in the BALB/c mice. The cell preparations did not protect the vaccinated mice from a live challenge (>300 50% lethal doses). Our results suggest that in BALB/c mice, a mixed T-helper-cell-like response to nonviable B. mallei is obtained, as demonstrated by a Th1- and Th2-like cytokine response and a Th2-like subclass immunoglobulin response. This may be the reason for the inability of the B. mallei cells that were examined as candidate vaccines to protect the mice from a live challenge.

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Immunology,Microbiology,Parasitology

Reference22 articles.

1. Acha P. N. and B. Szyfres. 1987. Zoonoses and communicable diseases common to man and animals 2nd edition. World Health Organization Washington D.C.

2. Boerner, P. 1882. A preliminary report on work by the Imperial Health Care Office leading to discovery of the glanders bacillus. Dtsch. Med. Wochenschr.52:707-708. (In German.)

3. Note: Burkholderia thailandensis sp. nov., a Burkholderia pseudomallei-like species

4. Centers for Disease Control and Prevention. 2000. Biological and chemical terrorism: strategic plan for preparedness and response. Morb. Mortal. Wkly. Rep.49(RR-4):1-14.

5. Centers for Disease Control and Prevention. 2000. Laboratory-acquired human glanders--Maryland. Morb. Mortal. Wkly. Rep.49:532-535.

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