Application of novel antibodies in pneumonia diagnosis and treatment
Wong, Wei Sheng
Date of Issue2017-05-17
School of Biological Sciences
Pneumonia is one of the leading causes for mortality and morbidity that exerts large healthcare and financial burden worldwide. Secondary bacterial infections resulting from Influenza infection are often associated with more severe pneumonia complication. Rapid emergences of antibiotic resistance pneumococci as well as lack of highly specific diagnostic tools pose major challenges in treatment and management of pneumonia. Pneumolysin is a highly conserved virulent factor which causes tissue damages and vascular leakages via its cytotoxic effect, making it an attractive therapeutic target. We have previously showed that enhancement of lung tissue recovery and reduction of inflammation-mediated damages can be achieved via immunoneutralization of c terminal region of angiopoietin-like 4 (cANGPTL4). Here, we aimed to examine the potential of antibody based treatment targeting host factors and pathogen virulent factors. Our findings demonstrated that combinatorial anti-cANGPTL4 and anti-pneumolysin antibody therapy significantly improved lung tissue integrity and increased survival rate of mice infected with S.pneumoniae and Influenza A. Furthermore, we showed that anti-pneumolysin mAb treatment prevented pneumolysin-mediated cell death in alveolar epithelial cells and restored phagocytic capability of monocytes in vitro. Taken together, our findings indicate a novel promising antibody based therapy for pneumonia which may help to combat the uprising antibiotic resistance crisis. Lastly, we concluded that serum samples were unsuited for cANGPTL4 biomarker diagnosis as no significant differences in serum cANGPTL4 expression levels were observed in non-pneumonia patients and pneumonia patients.
Final Year Project (FYP)
Nanyang Technological University