The secreted lipoprotein, MPT83, of Mycobacterium tuberculosis is recognized during human tuberculosis and stimulates protective immunity in mice

Autor: James A. Triccas, Sultana Mahmuda, Warwick J. Britton, Nicholas P. West, Fan F. Kao, Rachel Pinto
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Male
Bacterial Diseases
lcsh:Medicine
Antigen Processing and Recognition
Adaptive Immunity
Epitope
Mice
Cytotoxic T cell
Tuberculosis Vaccines
lcsh:Science
Immune Response
Mycobacterium bovis
Vaccines
Multidisciplinary
Vaccination
Immunizations
medicine.anatomical_structure
Infectious Diseases
Medicine
Female
Research Article
Tuberculosis
Infectious Disease Control
T cell
Immune Cells
Immunology
Antigen-Presenting Cells
Biology
Microbiology
DNA vaccination
Mycobacterium
Mycobacterium tuberculosis
Immune Activation
Adjuvants
Immunologic
Bacterial Proteins
Vaccine Development
medicine
Animals
Humans
Immunity to Infections
Microbial Pathogens
Antigens
Bacterial
lcsh:R
Immunity
Membrane Proteins
medicine.disease
biology.organism_classification
Virology
Mice
Inbred C57BL
Clinical Immunology
lcsh:Q
CD8
Zdroj: PLoS ONE, Vol 7, Iss 5, p e34991 (2012)
PLoS ONE
ISSN: 1932-6203
Popis: The long-term control of tuberculosis (TB) will require the development of more effective anti-TB vaccines, as the only licensed vaccine, Mycobacterium bovis bacille Calmette-Guérin (BCG), has limited protective efficacy against infectious pulmonary TB. Subunit vaccines have an improved safety profile over live, attenuated vaccines, such as BCG, and may be used in immuno-compromised individuals. MPT83 (Rv2873) is a secreted mycobacterial lipoprotein expressed on the surface of Mycobacterium tuberculosis. In this study, we examined whether recombinant MPT83 is recognized during human and murine M. tuberculosis infection. We assessed the immunogenicity and protective efficacy of MPT83 as a protein vaccine, with monophosphyl lipid A (MPLA) in dimethyl-dioctadecyl ammonium bromide (DDA) as adjuvant, or as a DNA vaccine in C57BL/6 mice and mapped the T cell epitopes with peptide scanning. We demonstrated that rMPT83 was recognised by strong proliferative and Interferon (IFN)-γ-secreting T cell responses in peripheral blood mononuclear cells (PBMC) from patients with active TB, but not from healthy, tuberculin skin test-negative control subjects. MPT83 also stimulated strong IFN-γ T cell responses during experimental murine M. tuberculosis infection. Immunization with either rMPT83 in MPLA/DDA or DNA-MPT83 stimulated antigen-specific T cell responses, and we identified MPT83(127-135) (PTNAAFDKL) as the dominant H-2(b)-restricted CD8(+) T cell epitope within MPT83. Further, immunization of C57BL/6 mice with rMPT83/MPLA/DDA or DNA-MPT83 stimulated significant levels of protection in the lungs and spleens against aerosol challenge with M. tuberculosis. Interestingly, immunization with rMPT83 in MPLA/DDA primed for stronger IFN-γ T cell responses to the whole protein following challenge, while DNA-MPT83 primed for stronger CD8(+) T cell responses to MPT83(127-135). Therefore MPT83 is a protective T cell antigen commonly recognized during human M. tuberculosis infection and should be considered for inclusion in future TB subunit vaccines.
Databáze: OpenAIRE
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