There is a need to improve the efficacy of the BCG vaccine against human and bovine tuberculosis. Previous data showed that boosting bacilli Calmette-Guerin (BCG)-vaccinated cattle with a recombinant attenuated human type 5 adenovirally vectored subunit vaccine (Ad5-85A) increased BCG protection and was associated with increased frequency of Ag85A-specific CD4 T cells post-boosting. Here, the capacity of Ag85A-specific CD4 T cell lines - derived before and after viral boosting - to interact with BCG-infected macrophages was evaluated. No difference before and after boosting was found in the capacity of these Ag85A-specific CD4 T cell lines to restrict mycobacterial growth, but the secretion of IL-10 in vitro post-boost increased significantly. Furthermore, cell lines derived post-boost had no statistically significant difference in the secretion of pro-inflammatory cytokines (IL-1β, IL-12, IFNγ or TNFα) compared to pre-boost lines. In conclusion, the protection associated with the increased number of Ag85A-specific CD4 T cells restricting mycobacterial growth may be associated with anti-inflammatory properties to limit immune-pathology.
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http://dx.doi.org/10.1016/j.vaccine.2018.03.068 | DOI Listing |
J Infect
August 2024
Department of Medicine, Division of Allergy and Immunology, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.
Background: A BCG booster vaccination administered via the respiratory mucosa may establish protective immune responses at the primary site of Mycobacterium tuberculosis infection. The primary objective of this trial was to compare the safety and immunogenicity of inhaled versus intramuscular administered ChAdOx1-85A.
Methods: We conducted a single-centre, randomised, double-blind, controlled phase 1 study (Swiss National Clinical Trials Portal number SNCTP000002920).
BackgroundAdenovirus-vectored (Ad-vectored) vaccines are typically administered via i.m. injection to humans and are incapable of inducing respiratory mucosal immunity.
View Article and Find Full Text PDFVaccine
March 2021
Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, and the Louisiana Vaccine Center, New Orleans, LA 70112, USA. Electronic address:
Bacille-Calmette-Guerin (BCG) has variable efficacy as an adult tuberculosis (TB) vaccine but can reduce the incidence and severity of TB infection in humans. We have engineered modified vaccinia Ankara (MVA) strain vaccine constructs to express the secreted mycobacterial proteins Ag85A and ESAT-6 (MVA-AE) and evaluated their immunogenicity and protective efficacy as mucosal booster vaccines for BCG given subcutaneously in early life. Intranasal delivery of MVA-AE to young adult mice induced CD4 and CD8 T cell responses to both Ag85A and ESAT-6 in lung mucosae.
View Article and Find Full Text PDFVaccine
March 2021
The Jenner Institute, University of Oxford, Old Road Campus Research Building, Roosevelt Drive, Oxford, United Kingdom. Electronic address:
A vaccine against tuberculosis (TB), a disease resulting from infection with Mycobacterium tuberculosis (M.tb), is urgently needed to prevent more than a million deaths per year. Bacillus Calmette-Guérin (BCG) is the only available vaccine against TB but its efficacy varies throughout the world.
View Article and Find Full Text PDFVaccine
January 2020
The Jenner Institute, University of Oxford, Oxford OX3 7DQ, UK. Electronic address:
Background: This phase I trial evaluated the safety and immunogenicity of a candidate tuberculosis vaccination regimen, ChAdOx1 85A prime-MVA85A boost, previously demonstrated to be protective in animal studies, in healthy UK adults.
Methods: We enrolled 42 healthy, BCG-vaccinated adults into 4 groups: low dose Starter Group (n = 6; ChAdOx1 85A alone), high dose groups; Group A (n = 12; ChAdOx1 85A), Group B (n = 12; ChAdOx1 85A prime - MVA85A boost) or Group C (n = 12; ChAdOx1 85A - ChAdOx1 85A prime - MVA85A boost). Safety was determined by collection of solicited and unsolicited vaccine-related adverse events (AEs).
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