Intranasal delivery of mRNA expressing newly identified Acinetobacter baumannii antigens protects against bacterial lung disease
Sophie L. Higham, Ziyin Wang, Valarmathy Murugaiah, J. Song, Chubicka Thomas, Hao Zhang, Uta Griesenbach, Eric W.F.W. Alton, Luke A. Granger, Andrea Flores Esparza, Beatriz Dias Barbieri, Paul G. Hitchen, Paul Kellam, Robin J. Shattock, Shiranee Sriskandan, Stephen T. Reece, John S. Tregoning
Abstract
Vaccines are central to the strategy to control antimicrobial resistant (AMR) bacterial infections; one multidrug resistant pathogen of particular concern is Acinetobacter baumannii. In this study we identified two novel A. baumannii antigens using mass spectrometry and phage expression: Oxa23 and PAL. These genes are highly conserved between different isolates of A. baumannii and recognised by convalescent human sera. We explored their protective immunity using two different vaccine platforms, recombinant outer membrane vesicles (rOMV) and mRNA. RNA vaccine immunised mice had significantly reduced bacterial load in their lower airways following challenge with carbapenem resistant A. baumannii, with Oxa23 providing better protection than PAL. We then compared routes of delivery and RNA vaccine platforms, demonstrating that intranasally delivery of mRNA encoding OXA-23 (formulated with GL67A) significantly reduced disease severity and enhanced bacterial clearance. These studies validate in silico identified antigens through challenge studies and novel mucosal vaccine delivery approaches.