Lactoferrin enhanced efficacy of the BCG vaccine to generate host protective responses against challenge with virulent Mycobacterium tuberculosis
| Autor: | Marian L. Kruzel, Robert L. Hunter, Margaret Olsen, Jeffrey K. Actor, Yogesh Bangale, Shen-An Hwang, Monika Budnicka, Katarzyna M. Wilk |
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| Rok vydání: | 2007 |
| Předmět: |
Tuberculosis
medicine.medical_treatment Population Immunization Secondary Biology Article Microbiology Mycobacterium tuberculosis Interferon-gamma Mice medicine Animals RNA Messenger Antigens education Lung Dosage Forms education.field_of_study Mycobacterium bovis General Veterinary General Immunology and Microbiology Tumor Necrosis Factor-alpha Lactoferrin Public Health Environmental and Occupational Health medicine.disease biology.organism_classification Mice Inbred C57BL Vaccination Infectious Diseases Organ Specificity Immunology BCG Vaccine biology.protein Molecular Medicine Female Adjuvant BCG vaccine Spleen |
| Zdroj: | Vaccine. 25:6730-6743 |
| ISSN: | 0264-410X |
| Popis: | Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a disease with world wide consequences, affecting nearly a third of the world's population. The established vaccine for TB, an attenuated strain of Mycobacterium bovis Calmette Guerin (BCG), has existed since 1921. Lactoferrin, an iron-binding protein found in mucosal secretions and granules of neutrophils was hypothesized to be an ideal adjuvant to enhance the efficacy of the BCG vaccine, specifically because of previous reports of lactoferrin enhancement of IL-12 production from macrophages infected with BCG. Different vaccination protocols were investigated for generation of host protective responses against MTB infection using lactoferrin admixed to the BCG vaccine. Resulting effects demonstrate that BCG/lactoferrin increased host protection against MTB infection by decreasing organ bacterial load and reducing lung histopathology; significant reduction in tissue CFUs and pathology were observed post-challenge compared to those seen with BCG alone. Addition of lactoferrin to the vaccine led to reduced pathological damage upon subsequent infection with virulent MTB, with positive results demonstrated when admixed in oil-based vehicle (incomplete Freund's adjuvant, IFA) or when given with BCG in saline. The observed post-challenge results paralleled increasing production of IFN-gamma and IL-6, but only limited changes to proinflammatory mediators TNF-alpha or IL-1beta from BCG-stimulated splenocytes. Overall, these studies indicate that lactoferrin is a useful and effective adjuvant to improve efficacy of the BCG vaccine, with potential to reduce related tissue damage and pulmonary histopathology. |
| Databáze: | OpenAIRE |
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