Individual-level factors associated with variation in mycobacterial-specific immune response: Gender and previous BCG vaccination status

Tuberculosis (Edinb). 2016 Jan:96:37-43. doi: 10.1016/j.tube.2015.10.002. Epub 2015 Nov 11.

Abstract

Introduction: A more effective tuberculosis (TB) vaccine is needed to eliminate TB disease. Many new vaccine candidates enhance the immunogenicity of the existing vaccine, Bacillus Calmette-Guérin (BCG). Understanding BCG induced immune variation is key to developing a new vaccine.

Aims: We aimed to establish if individual-level covariates were associated with cell-mediated immune response (interferon gamma (IFN-γ)) at vaccine trial enrolment (baseline) in a long-term retrospective analysis (LTR) and after BCG vaccination in a short-term prospective analysis (STP).

Methods: Four covariates were analysed: gender, country, BCG vaccination history and monocyte/lymphocyte cell count ratio. Univariable and multivariable linear regression were conducted on IFN-γ response at baseline for LTR, and area under the curve (AUC), 24 week and peak IFN-γ response for STP.

Results: Previous BCG vaccination was strongly associated with higher IFN-γ response at baseline (LTR analysis) (p-values < 0.05). Being male showed a weak association with higher baseline response (p-value = 0.1). BCG revaccination was strongly associated with a larger response increase than primary-vaccination (AUC & peak p-values < 0.01), but did not differ at 24 weeks (STP analysis). All other covariates were non-significant (p-values > 0.1).

Conclusion: This analysis suggests that previous BCG vaccination and gender are associated with durable IFN-γ responses. Vaccine trials may need to stratify by BCG vaccination history and gender.

Keywords: BCG; IFN-γ; Immune response; Tuberculosis.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Adult
  • Area Under Curve
  • BCG Vaccine / administration & dosage
  • BCG Vaccine / immunology*
  • Biomarkers / blood
  • Cross-Sectional Studies
  • Enzyme-Linked Immunospot Assay
  • Female
  • Humans
  • Immunity, Cellular*
  • Immunization Schedule
  • Interferon-gamma / blood
  • Interferon-gamma / immunology*
  • Interferon-gamma Release Tests
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mycobacterium tuberculosis / immunology*
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve
  • Retrospective Studies
  • Sex Factors
  • Time Factors
  • Vaccination*
  • Young Adult

Substances

  • BCG Vaccine
  • Biomarkers
  • IFNG protein, human
  • Interferon-gamma