Studies of Humoral and Cell-Mediated Immune Protection During Mycobacterium Tuberculosis Infection in Human Population in an Endemic Setting, 2014

Tuberculosis (TB) causes an estimated 2 million people per year globally. However, despite technological advances of the 21st century, there are no efficacious vaccines that prevent TB transmission. The protective efficacy of BCG varies from zero to 80%, depending on the study population. Immune effector mechanisms that lead to protection or susceptibility are poorly known. It is generally believed that T cell immunity is critical for protection against Mtb. However, the role of humoral immunity in protection against Mtb infection has been neglected based on early classical experiments that lacked standard protocols, and the Th1/Th2 paradigm. In recent years, however, major discrepancies in this paradigm have been observed. A substantial body of data suggest that there is synergy and mutual interdependence between the two arms of acquired immunity. Studies on B cell deficient mice and SCID mice and responses to specific mycobacterial antigens in human subjects indicate that specific antibodies are not only protective but also modulate CMI against TB. This is a prospective study in which TB patients, their contacts (>100h), and endemic controls (CCs) were selected from TB endemic communities, and their immune status determined. The immune profile of TB patients was determined before treatment, and six months and 12 months after treatment. The immune profile of HHCs and CCs was determined upon entry into the study and at 12 month intervals for two years. RT-PCR was used to determine the level of cytokine mRNA, whereas ELISA was employed to determine the level of specific cytokine and antibody responses. An appropriate statistical model was used to determine association of immune effector molecules with clinical disease or immune protection. Rapid TB diagnostic tests (under development in Norway) were evaluated. This project was the first of its kind to explore the protective role of antibodies in human cohorts in an endemic setting.