“Finish with tuberculosis by 2030 is one of the objectives of sustainable development goals of recent adoption of the World Health Organization,” said Lenette Lu, MD, PhD, of the Ragon Institute and Hospital ( MGH) Massachusetts General Department of Medicine, a primary co-author of Cellreport. “A more effective vaccine against tuberculosis could contribute substantially towards that goal, which affects nearly one in three people in the world who are infected and to address the main cause of death for people infected with HIV.”
The only currently available preventive against infection with TB bacteria – BCG – has been available since the 1920s; but its efficacy against pulmonary TB, the most common form of the disease, has always been uncertain. BCG is believed to work by stimulating cellular immunity, which is performed by specialized immune cells including T cells and macrophages that are infected directly by tuberculosis bacteria. Previous research on a possible role of antibodies in the immune response to tuberculosis have had conflicting results, but the Ragon team – led by Galit Alter, PhD, Department of Medicine at MGH and Sarah Fortune, MD, of Harvard University TH Chan School of Public Health -. Used a novel approach
In addition to binding to its target and marked for destruction by the immune system pathogen, 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 outlines specific antibodies TB from 22 people with latent TB and 20 with active TB for 70 different characteristics associated with antibody-mediated function Fc. First they identified nine characteristics that differed between the antibodies of the two groups of participants, and research identified the biomarker that better distinguish between them.
A key regulator of immune function mediated by Fc antibody is the addition of compounds called glycans, composed of sugar molecules; and no clear differences in glycosylation patterns of antibodies clearly distinguish latent TB antibodies active TB were found. To confirm these results in the initial group of participants, who came from South Africa, the team conducted a similar analysis of antibodies from 20 individuals from Texas and Mexico – half and half with latent with active TB – and he had the same results. Other experiments revealed that application of antibodies latent TB human macrophages infected with tuberculosis not only increased the activation of several antimicrobial processes, but also reduced the survival of the tuberculosis bacteria.
Co-senior author Amy Chung, PhD, now at Doherty Peter Institute for Infection and Immunity in Melbourne, Australia – a joint venture between the University of Melbourne and the Melbourne Royal Hospital – explains, “This is an area completely new immunological research in tuberculosis, as these antibodies recognize not only the infection but also recruit immune to address him cells. people with latent infection are inactive for a reason disease, and whether the antibodies are playing a role in the control of infection, the mechanism used could be exploited for future vaccine development. “
Alter, associate professor of medicine at the Faculty of Harvard Medical adds. “The diagnostic potential of these findings should not be overlooked Detection of modifications related to the Fc-specific antibody TB could easily translate into rapid, low cost at the point of care diagnostics that could have a huge impact on public health, especially in those parts of the world where tuberculosis is endemic. “
“These findings – which could lead to major advances in the fight against one of the oldest diseases of mankind – would have been impossible without visionary philanthropists like Terry and Susan Ragon, whose major gift created the Ragon Institute in 2009 and Mark and Lisa Schwartz, whose long-term support provided initial funding for the work of Dr. Alter “says Peter Slavin, MD, president of the Massachusetts General hospital, where the Ragon Institute administratively is based.
Tracy Rosebrock, PhD, of the Harvard School Chan is also a co-lead author of the Cell paper. The study was supported by the National Institutes of Health grants R01 AI080289 and AI102660 and AI007387 T32, DARPA grant BAA-11-65, the Harvard Center for AIDS Research, the Bill and Melinda Gates Foundation, National Health and Medical Research Council ( australia) APP1036470 grant and support from the Bill and Melinda Gates Foundation, the Foundation of Family Pozen, the Doris Duke medical Research Foundation and the Burroughs Wellcome Foundation, along with funding from the Ragon Institute.