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

Abstract

Acinetobacter baumannii causes pneumonias, bacteremias, and skin and soft tissue infections, primarily in the hospitalized setting. The incidence of infections caused by A. baumannii has 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 of A. baumannii infection. In this study, an outer membrane complex vaccine consisting of multiple surface antigens from the bacterial membrane of A. baumannii was 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 of A. 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.

Severe Acinetobacter baumannii Sepsis Is Associated with Elevation of Pentraxin 3

“…In vivo pathogenesis comparison between A. baumannii strains. Traditionally, bacterial sepsis models used for study of A. baumannii utilize porcine mucin to enhance virulence of the bacterium through inhibition of phagocytosis (13,43,44). Consequently, LD 50 values as low as 10 3 to 10 4 CFU have been reported, with time to death (TTD) near 1 week postchallenge (13,14).…”

Physiology and Pathology of Multidrug-Resistant Bacteria: Antibodies- and Vaccines-Based Pathogen-Specific Targeting

“…Vaccine made of outer membrane complexes (OMCs) from A. baumannii induced protective humoral and cellular immune responses against murine sepsis model [158]. Similarly, passive transfer of antiserum from immunized murine to naive mice rescued these mice from…”

Are we closing in on an "elusive enemy"? The current status of our battle withAcinetobacter baumannii

“…[26][27][28][29] Of tremendous import, an Omp vaccine with multiple surface antigens from the bacterial membrane of A. baumannii elicited protective and therapeutic humoral and cellular responses in a murine sepsis model. 30 How well will this serve as a start to a vaccine remains to be seen.…”