A recent study published in Scientific Reports has identified a new population of immune cells that could be pivotal in developing an alternative tuberculosis (TB) vaccine. The research, led by Dr. Charles Kyriakos Vorkas from the Renaissance School of Medicine at Stony Brook University, suggests these findings may guide future TB vaccines and immune therapies.
TB continues to pose a significant global health challenge, with over 10 million cases reported annually according to the World Health Organization. The disease remains the leading cause of infectious morbidity and mortality worldwide due to Mycobacterium tuberculosis.
The study focused on innate immune cells known as Natural Killer (NK) cells that express CD8a on their surface. These cells were found to react to TB exposure and infection within a high-risk cohort in Port-au-Prince, Haiti. This cohort was part of a National Institutes of Health-funded TB Research Unit project conducted between 2015 and 2018.
Dr. Vorkas explained, "Our research shows a specialized role for these CD8a+ NK cells, including progressive depletion from blood during asymptomatic infection and active TB disease." He noted their enhanced responsiveness to cytokines and dependence on major histocompatibility complex (MHC) Class I expression.
The study's insights align with other recent findings in the Journal of Experimental Medicine about CD8aa+ lymphocytes' role in BCG-induced protection against TB in non-human primates. A significant portion of these protective lymphocytes are NK cells.
Currently, Bacille-Calmette Guérin (BCG) is the only approved TB vaccine but lacks long-lasting effects in adults. Experimental vaccines targeting conventional T cells have not met efficacy expectations, possibly due to insufficient correlation with primary infection prevention.
The research team also observed parallels between NK cell depletion during disease progression in other conditions like cancer and multiple sclerosis. Future research aims to explore how NK cells recognize TB-derived proteins through Killer immunoglobulin-like Receptors (KIRs).
Dr. Vorkas suggested that if NK cells can recognize specific antigens via KIRs similarly to T cell receptors, it could revolutionize vaccine design and immune therapies for TB.
This study was conducted with support from Memorial Sloan Kettering Cancer Center labs and funded by NIH grants including NIAID K08AI132739, R21SI171578, R21AI83259, along with a Potts Memorial Foundation Award.