Vaccination with outer membrane complexes elicits rapid protective immunity to multidrug-resistant Acinetobacter baumannii.
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.
Unit of Infectious Disease, Microbiology, and Preventive Medicine, Hospitales Universitarios Virgen del Rocío, Edificio Laboratorio Anexo Caracola, Avenida Manuel Siurot s/n, 41013 Seville, Spain. mcconnell.mike75@gmail.com
Michael J
MJ
McConnell
Juan
J
Domínguez-Herrera
Younes
Y
Smani
Rafael
R
López-Rojas
Fernando
F
Docobo-Pérez
Jerónimo
J
Pachón
D000151:Acinetobacter Infections / Q000382:microbiology / Q000517:prevention & control*; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000276:immunology*; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors
D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines