Variability between countries in cytokine responses to BCG vaccination: what impact might this have on protection?

Abstract

*All authors contributed equally to this manuscript. In 2010, there were an estimated 8.8 million incident cases of TB and 1.4 million deaths globally despite the widespread use of BCG [101]. With the aim of elimination of TB by 2050, there is a concerted drive to combine interventions in order to improve diagnosis, prevent infection, treat active disease and reduce the risk factors for TB [102]. With the rising burden of drug-resistant strains of TB and with TB susceptibility in those with HIV/AIDS, there is an urgent need for new effective vaccines that work for all forms of TB in preand post-exposed individuals of all ages in all parts of the world. Whilst there are promising signs in TB vaccine development [1], there are still many unanswered questions, in particular as to what constitutes a protective immune response. Geographic variations in protective immunity induced by the current vaccine, BCG [2], are still poorly understood, and without biomarkers of protection, there are many challenges ahead to identify and test potential vaccines for TB globally. Smaller immunological studies have shown variability in cytokine responses to BCG vaccination between countries, including between BCG-vaccinated adolescents and infants in Malawi and the UK [3–5]. Whereas UK adolescents made strong IFN-γ responses to Mycobacterium tuberculosis (Mtb) purified protein derivative (PPD) post-vaccination, Malawian adolescents and young adults who were presensitized to PPD failed to show a significant increase [3]. Malawian infants also produced weaker IFN-γ responses following BCG vaccination than infants in the UK [4,5]. Three questions arise from these observations: are the differences real, are they important and what implications might they have on protection induced by BCG and future vaccines?