+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Alternative BCG delivery strategies improve protection against Mycobacterium tuberculosis in non-human primates: Protection associated with mycobacterial antigen-specific CD4 effector memory T-cell populations



Alternative BCG delivery strategies improve protection against Mycobacterium tuberculosis in non-human primates: Protection associated with mycobacterial antigen-specific CD4 effector memory T-cell populations



Tuberculosis 101: 174-190



Intradermal (ID) BCG injection provides incomplete protection against TB in humans and experimental models. Alternative BCG vaccination strategies may improve protection in model species, including rhesus macaques. This study compares the immunogenicity and efficacy of BCG administered by ID and intravenous (IV) injection, or as an intratracheal mucosal boost (ID + IT), against aerosol challenge with Mycobacterium tuberculosis Erdman strain. Disease pathology was significantly reduced, and survival improved, by each BCG vaccination strategy, relative to unvaccinated animals. However, IV induced protection surpassed that achieved by all other routes, providing an opportunity to explore protective immunological mechanisms using antigen-specific IFN-γ ELISpot and polychromatic flow cytometry assays. IFN-γ spot forming units and multifunctional CD4 T-cell frequencies increased significantly following each vaccination regimen and were greatest following IV immunisation. Vaccine-induced multifunctional CD4 T-cells producing IFN-γ and TNF-α were associated with reduced disease pathology following subsequent M.tb challenge; however, high frequencies of this population following M.tb infection correlated with increased pathology. Cytokine producing T-cells primarily occupied the CD4 transitional effector memory phenotype, implicating this population as central to the mycobacterial response, potentially contributing to the stringent control observed in IV vaccinated animals. This study demonstrates the protective efficacy of IV BCG vaccination in rhesus macaques, offering a valuable tool for the interrogation of immunological mechanisms and potential correlates of protection.

(PDF emailed within 0-6 h: $19.90)

Accession: 057164782

Download citation: RISBibTeXText

PMID: 27865390

DOI: 10.1016/j.tube.2016.09.004


Related references

Recombinant adenovirus delivery of calreticulin-ESAT-6 produces an antigen-specific immune response but no protection against a Mycobacterium tuberculosis challenge. Scandinavian Journal of Immunology 75(3): 259-265, 2012

CD28 costimulation enhances the sensitivity of the ELISPOT assay for detection of antigen-specific memory effector CD4 and CD8 cell populations in human diseases. Journal of Immunological Methods 285(2): 223-235, 2004

Biologically active components from mycobacterial cell walls. IV. Protection of mice against aerosol infection with virulent mycobacterium tuberculosis. Cellular Immunology 16(1): 1-10, 1975

Enhancement of human antigen-specific memory T-cell responses by interleukin-7 may improve accuracy in diagnosing tuberculosis. Clinical and Vaccine Immunology 15(10): 1616-1622, 2008

Functional, Antigen-Specific Stem Cell Memory (TSCM) CD4+ T Cells Are Induced by Human Mycobacterium tuberculosis Infection. Frontiers in Immunology 9: 324-324, 2018

Biologically active components from mycobacterial cell walls part 4 protection of mice against aerosol infection with virulent mycobacterium tuberculosis. Cellular Immunology: 1-10, 1975

Association of mycobacterial antigen-specific CD4(+) memory T cell subsets with outcome of pulmonary tuberculosis. Journal of Infection 60(2): 133-139, 2010

Detection of antigen-specific memory/effector T cell populations by multiparameter cytokine flow cytometry. Cytometry 59A(1): 33, 2004

A recombinant mycobacterial protein antigen common to mycobacterium leprae mycobacterium tuberculosis and mycobacterium bovis bcg is presented to human t cells by hla dr4 dw14 molecules. Scandinavian Journal of Immunology 32(4): 409, 1990

DNA vaccine using hemagglutinating virus of Japan-liposome encapsulating combination encoding mycobacterial heat shock protein 65 and interleukin-12 confers protection against Mycobacterium tuberculosis by T cell activation. Vaccine 24(8): 1191-1204, 2005

Mycobacterial growth inhibition in murine splenocytes as a surrogate for protection against Mycobacterium tuberculosis (M. tb). Tuberculosis 93(5): 551-557, 2014

Immunological memory transferred with CD4 T cells specific for tuberculosis antigens Ag85B-TB10.4: persisting antigen enhances protection. Plos One 4(12): E8272-E8272, 2010

Protection by and maintenance of CD4 effector memory and effector T cell subsets in persistent malaria infection. Plos Pathogens 14(4): E1006960-E1006960, 2018

Effect of attenuation of Treg during BCG immunization on anti-mycobacterial Th1 responses and protection against Mycobacterium tuberculosis. Plos One 3(7): E2833-E2833, 2008

Cytotoxicity of human mycobacterium tuberculosis specific cd4 plus t cell clones for monocytes pulsed with mycobacterial antigens. Clinical Research 38(2): 269A, 1990