title: Lactoferrin augments BCG vaccine efficacy to generate T helper response and subsequent protection against challenge with virulent Mycobacterium tuberculosis.
abstract: The ability to control intracellular Mycobacterium tuberculosis (MTB) infection relies on cellular immunity and generation of a strong T-cell helper 1 (T(H)1) response. Lactoferrin, an iron-binding protein with immune regulatory functions, was investigated as an adjuvant to boost Mycobacterium bovis Bacillus Calmette-Guerin (BCG) efficacy. Lactoferrin was initially shown to augment IL-12(p40) production from macrophages stimulated with LPS. A single immunization of mice with Lactoferrin as an adjunct adjuvant resulted in amplified splenocyte proliferative response to heat-killed BCG, and elevated IL-12(p40) production with increased relative ratios of IL-12/IL-10. Furthermore, splenocyte recall response to HK-BCG was augmented for proinflammatory mediators, TNF-alpha, IL-1beta, and IL-6, approaching responses generated to complete Freund's adjuvant (CFA) immunized controls. Specific responses were identified, with significant elevation of IFN-gamma generated during antigenic recall. Subsequent aerosol challenge of Lactoferrin adjuvant immunized mice with virulent M. tuberculosis revealed decreased mycobacterial loads in the lung, and limitation of organism dissemination to a peripheral organ (spleen). These studies indicate that Lactoferrin can act as an adjunct adjuvant to augment cellular immunity and boost BCG efficacy for protection against subsequent challenge with virulent MTB.
authors.affiliation: MSB 2.214 Department of Pathology and Laboratory Medicine-Program in Molecular Pathology, 6431 Fannin, UTHHSC, University of Texas-Houston Medical School, Houston, TX 77030, USA.
authors.forename: Shen-An
authors.initials: SA
authors.lastname: Hwang
authors.forename: Marian L
authors.initials: ML
authors.lastname: Kruzel
authors.forename: Jeffrey K
authors.initials: JK
authors.lastname: Actor
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000276:immunology* / Q000494:pharmacology; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007781:Lactoferrin / Q000276:immunology* / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009163:Mycobacterium bovis / Q000276:immunology; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000382:microbiology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D014774:Virulence
chemical_list: D001500:BCG Vaccine; D016207:Cytokines; D008070:Lipopolysaccharides; D018664:Interleukin-12; D007371:Interferon-gamma; D007781:Lactoferrin