Adjunct antibody therapy for severe antibiotic-resistant Acinetobacter baumannii infections

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Acinetobacter baumannii is a major cause of severe infections in Asian LMICs and has high levels of resistance to multiple antibiotics. To counter the threat of A. baumannii infections in LMICs will require the rapid introduction of new therapies which don't stimulate antibiotic resistance. To address this need we will develop an adjunct multivalent antibody therapy against protein antigens to promote A. baumannii clearance and improve antibiotic efficacy. We will use our recent A. baumannii genome data for 232 strains isolated from Thai patients to construct a comprehensive protein microarray of conserved proteins. This will be probed with sera from Thai subjects recovering from A. baumannii infection and from mice exposed to non-fatal A. baumannii infection to identify antigenic proteins. RNAseq of bacteria recovered from mouse and ex-vivo blood models of infection will identify A. baumannii proteins that are highly expressed during infection and in response to antibiotics and therefore are suitable targets for an antibody therapy. From these data, we will select protein antigens for testing as targets for antibody therapy using in vitro immune assays and mouse models of A. baumannii infection. The most effective antigens will be combined for a multivalent antibody therapy. To better define the role of adjunct antibody therapy we will prospectively collect clinical data on 100 Thai patients with proven A. baumannii infection. In addition, we will purify from these subjects antibody the above data demonstrate are effective at controlling A. baumannii infection for efficacy and dose response testing using a human blood infection model. Overall, the project will develop a novel antibody adjunct therapy for use in severe A. baumannii infections in LMICs that can help combat antibiotic resistance, and provide the clinical and in vitro proof of principle data important for further clinical development of the therapy