A novel recombinant human lactoferrin augments the BCG vaccine and protects alveolar integrity upon infection with Mycobacterium tuberculosis in mice.
Lactoferrin, an iron binding glycoprotein, possesses multiple immune modulatory activities, including the ability to promote antigen specific cell-mediated immunity. Previous studies showed that adding bovine lactoferrin to the BCG vaccine (an attenuated strain of Mycobacterium bovis Bacillus Calmette Guerin) resulted in increased host protective responses upon subsequent challenge with virulent Erdman Mycobacterium tuberculosis (MTB) in mice. The studies outlined here investigate utility of a novel recombinant human lactoferrin to enhance the BCG vaccine and protect against alveolar injury during experimental MTB infection in mice. Sialylated and non-sialylated forms of the recombinant human lactoferrin (rhLF), glycoengineered in yeast (Pichia pastoris) and expressing humanized N-glycosylation patterns, were examined for their ability to enhance efficacy of the BCG vaccine in a murine TB model system. Results indicated that the sialylated form of the recombinant human lactoferrin generated increased antigen specific recall responses to BCG antigens. Furthermore, augmented protection was demonstrated using the sialylated lactoferrin adjuvant with BCG, resulting in significant reduction in associated pathology following challenge with virulent organisms.
Hwang
Shen-An
SA
Department of Pathology, Medical School, University of Texas-Houston Medical School, Houston, TX 77030, USA.
Wilk
Katarzyna
K
Kruzel
Marian L
ML
Actor
Jeffrey K
JK
D000276:Adjuvants, Immunologic / Q000627:therapeutic use; D000818:Animals; D001500:BCG Vaccine / Q000627:therapeutic use*; D002352:Carrier Proteins / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007111:Immunity, Cellular; D007781:Lactoferrin; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011650:Pulmonary Alveoli / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D011994:Recombinant Proteins / Q000276:immunology / Q000627:therapeutic use; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*
D000276:Adjuvants, Immunologic; D001500:BCG Vaccine; D002352:Carrier Proteins; C490098:LTF protein, human; D011994:Recombinant Proteins; D007781:Lactoferrin