Impact of individual-level factors on Ex vivo mycobacterial growth inhibition: Associations of immune cell phenotype, cytomegalovirus-specific response and sex with immunity following BCG vaccination in humans

• Published in: Tuberculosis (Edinburgh, Scotland) Vol. 119; p. 101876
• Main Authors: Prabowo, Satria A., Smith, Steven G., Seifert, Karin, Fletcher, Helen A.
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.12.2019; Elsevier Science Ltd
• Subjects: Bacillus Calmette-Guerin vaccine; BCG; Cell activation; Clinical trials; Cytomegalovirus; Females; Growth inhibition assay; Health risks; Immune response; Immune system; Immunogenicity; Lymphocytes T; Males; NK cell; Peripheral blood; Phenotypes; Risk analysis; Risk factors; Sex; Tuberculosis; Tuberculosis vaccine; Vaccine efficacy; Vaccines; Growth inhibition assay; Cytomegalovirus; Tuberculosis vaccine; BCG; Sex; NK cell
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2019.101876

Understanding factors associated with varying efficacy of Bacillus Calmette-Guérin (BCG) would aid the development of improved vaccines against tuberculosis (TB). In addition, investigation of individual-level factors affecting mycobacterial-specific immune responses could provide insight into confounders of vaccine efficacy in clinical trials. Mycobacterial growth inhibition assays (MGIA) have been developed to assess vaccine immunogenicity ex vivo and provide a measure of immune function against live mycobacteria. In this study, we assessed the impact of immune cell phenotype, cytomegalovirus (CMV)-specific response and sex on ex vivo growth inhibition following historical BCG vaccination in a cohort of healthy individuals (n = 100). A higher frequency of cytokine-producing NK cells in peripheral blood was associated with enhanced ex vivo mycobacterial growth inhibition following historical BCG vaccination. A CMV-specific response was associated with T-cell activation, a risk factor for TB disease and we also observed an association between T-cell activation and ex vivo mycobacterial growth. Interestingly, BCG-vaccinated females in our cohort controlled mycobacterial growth better than males. In summary, our present study has shown that individual-level factors influence capacity to control mycobacterial growth following BCG vaccination and the MGIA could be used as a tool to assess how vaccine candidates may perform in different populations.