Presenter of 1 Presentation
O041 - BROADLY REACTIVE ANTI-PNEUMOCOCCAL ANTIBODIES FOR DISEASE TREATMENT (ID 362)
Abstract
Background
Streptococcus pneumoniae remains a leading cause of bacterial pneumonia. Despite widespread vaccination, a rise in infection and antibiotic resistance among nonvaccine serotypes has contributed to high disease incidence. Human monoclonal antibodies (mAbs) are gaining traction for the prevention and treatment of infectious diseases, and could provide an alternative and/or conjunctive option for pneumococcal disease treatment.
Methods
We isolated the first human mAbs to the pneumococcal histidine triad protein (PhtD). Binding analysis was completed by ELISA and biolayer interferometry. The serotype breadth of each mAb was determined using ELISAs and flow cytometry. mAbs were tested in several mouse challenge models, and we conducted several in vivo studies to determine the mechanism of pneumococcal mAb protection.
Results
mAbs PhtD3, PhtD6, PhtD7, and PhtD8 target diverse epitopes, which were correlated to serotype breadth. Prophylactic administration of mAbs PhtD3 and PhtD7 protected mice in intranasal and intravenous infection models with pneumococcal serotypes 3 and 4. mAb PhtD3 rescued mice when administered 24 hrs after infection, and a PhtD3/PhtD7 cocktail had enhanced protective efficacy. mAb PhtD3 efficacy was dependent on macrophages and complement, but not neutrophils, and mAb PhtD3 reduced the bacterial burden in mouse lungs and blood. Furthermore, mAb PhtD3 prolonged the survival of mice in an influenza/pneumococcal co-infection model.
Conclusions
We demonstrated that human mAbs to PhtD target diverse epitopes and protect against lethal pneumococcal infection. Ongoing studies include the isolation of human mAbs to additional protein antigens, optimizing mAb delivery, testing of additional mAb cocktails, and determining mAb efficacy in additional viral secondary infection models.