Vaccination with Outer Membrane Complexes Elicits Rapid Protective Immunity to Multidrug-ResistantAcinetobacter baumannii

Abstract

ABSTRACTAcinetobacter baumanniicauses pneumonias, bacteremias, and skin and soft tissue infections, primarily in the hospitalized setting. The incidence of infections caused byA. baumanniihas increased dramatically over the last 30 years, while at the same time the treatment of these infections has been complicated by the emergence of antibiotic-resistant strains. Despite these trends, no vaccines or antibody-based therapies have been developed for the prevention ofA. baumanniiinfection. In this study, an outer membrane complex vaccine consisting of multiple surface antigens from the bacterial membrane ofA. baumanniiwas developed and tested in a murine sepsis model. Immunization elicited humoral and cellular responses that were able to reduce postinfection bacterial loads, reduce postinfection proinflammatory cytokine levels in serum, and protect mice from infection with human clinical isolates ofA. baumannii. A single administration of the vaccine was able to elicit protective immunity in as few as 6 days postimmunization. In addition, vaccine antiserum was used successfully to therapeutically rescue naïve mice with established infection. These results indicate that prophylactic vaccination and antibody-based therapies based on an outer membrane complex vaccine may be viable approaches to preventing the morbidity and mortality caused by this pathogen.