“A more effective vaccine against TB could substantially contribute towards that goal, impacting the nearly one in three people worldwide who are infected and addressing the leading killer of individuals infected with HIV.” The only currently available preventive against infection with the TB bacteria – the BCG vaccine – has been available since the 1920s; but its effectiveness against pulmonary TB, the most common form of the disease, has always been uncertain.
Previous investigations into a possible role for antibodies in the immune response to TB have had conflicting results, but the Ragon team – led by Galit Alter, Ph.D., of MGH Department of Medicine and Sarah Fortune, MD, of the Harvard T.H. Chan School of Public Health – used a novel approach.
In addition to binding to their target pathogens and marking them for destruction by the immune system, antibodies also directly stimulate pathogen-killing cells of the innate immune system by binding to a cell-surface protein called the Fc receptor.
The Ragon team profiled TB-specific antibodies from 22 individuals with latent TB and 20 with active TB for 70 different features associated with Fc-mediated antibody function. They first identified nine characteristics that differentiated between antibodies of the two groups of participants, and further investigation identified the biomarker that best distinguished between them.
A key regulator of the Fc-mediated immune function is the addition to antibodies of compounds called glycans, made up of sugar molecules; and distinct differences in glycosylation patterns were found to clearly distinguish latent TB antibodies from active TB antibodies.
To confirm these results in the initial group of participants, who were from South Africa, the team conducted a similar analysis of antibodies from 20 individuals from Texas and Mexico – half with latent and half with active TB – and had the same results. Further experiments revealed that application of latent TB antibodies to TB-infected human macrophages not only increased the activation of several antimicrobial processes but also reduced the survival of the TB bacteria.
Press release: Antibody function may help keep tuberculosis infection under control
Journal article: http://dx.doi.org/10.1016/j.cell.2016.08.072