Inhibition of Mycobacterium Tuberculosis Growth by Monoclonal Antibodies Isolated from an Actively Infected Patient

Recently, due to increasing rates of antibiotic-resistant strains, Mycobacterium tuberculosis (Mtb) is re-emerging as a global health threat. Evidence suggests that naturally occurring anti-Mtb antibodies elicited in patients during infection can be protective. Thus, our goal was to isolate anti-Mtb monoclonal antibodies (mAbs) from infected patients and test their effect on Mtb. Accordingly, a cohort of 26 actively Mtb-infected patients was recruited from Shmuel Harofe Hospital, Israel. These patients displayed high anti-Mtb serum antibodies compared to uninfected controls. To map the targets of the sera we expressed six surface Mtb virulence-related proteins and tested the patients’ serum responses against them. Patient 109004 presented the highest overall response to PstS1, an ABC phosphate transporter responsible for Mtb phosphate metabolism. To characterize the antibodies against PstS1 on a monoclonal level we single-cell sorted PstS1- specific B cells from patient 109004 and sequenced their membrane antibodies. We identified five distinct B cell clones, of which, we produced five mAbs. All the antibodies bound PstS1 with high affinity, as well as binding to the whole attenuated and pathogenic bacteria. mAbs P4-36 and P4-163 inhibited in vitro growth of pathogenic Mtb in human whole blood cells. In addition, both P4-36 and P4-163 showed a modest level of protection in vivo when administered to mice before bacterial challenge. P4-36 and P4-163 are human inhibiting anti-Mtb mAbs and they may represent a new class of potential anti-Mtb therapeutics. Additionally, their target epitopes could potentially serve as new vaccine modalities.