Outer membrane vesicles as an acellular vaccine against Acinetobacter baumannii

Acinetobacter baumannii produces different types of infections including pneumonia, meningitis, and bloodstream infections. The optimal treatment of these infections has been complicated by the global emergence of multidrug resistant strains, requiring the development of novel approaches for treatment and prevention. Outer membrane vesicles are outpouchings of the bacterial outer membrane that are secreted from numerous pathogenic Gram-negative bacteria. In the present study, we describe the isolation of outer membrane vesicles from A. baumannii and their use as a vaccine in a mouse model of disseminated sepsis. Immunization produced a robust antibody response against multiple bacterial antigens which consisted of antigen-specific IgG and IgM. In addition, both IgG1 and IgG2c subtypes were produced by immunization. Immunized mice had lower tissue bacterial loads and lower serum levels of the pro-inflammatory cytokines IL-6 and IL-1β post-infection compared to control mice. Importantly, vaccination protected mice from challenge with the ATCC 19606 strain and provided protection against two clinical isolates, including a pan-resistant strain. These results indicate that vaccination with outer membrane vesicles may be a viable strategy for preventing A. baumannii infection. © 2011 Elsevier Ltd.This work was funded by the Consejería de Innovación, Ciencia y Empresa de la Junta de Andalucía P08-CTS-03842 awarded to JP and by the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III – co-financed by European Development Regional Fund “A way to achieve Europe” ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD06/0008/0000). MJM is supported by the Subprograma Juan de la Cierva from the Ministerio de Ciencia y Innovación of Spain. GB was funded by FIS grants PI081613, PS09/00687, and PS07/90 and grant 08CSA064916PR from Xunta de Galicia. Carlos Rumbo is a recipient of a scholarship from Instituto de Salud Carlos III.Peer Reviewe