Intranasal immunization protects against Acinetobacter baumannii-associated pneumonia in mice.
Multidrug-resistant Acinetobacter baumannii has become an important causative agent of healthcare associated infections. Hospital- and community-acquired pneumonia is the most common clinical manifestation of A. baumannii infection worldwide and is often associated with high mortality. Most experimental vaccine studies to date have evaluated vaccines against systemic A. baumannii infections following systemic immunization. We recently demonstrated that a mouse model of respiratory A. baumannii infection using the strain LAC-4 results in disease progression that is similar to that observed in humans. Here we used this model in conjunction with an inactivated whole cell vaccine to evaluate the feasibility of developing protective mucosal vaccines against respiratory A. baumannii infection and to investigate the potential mechanism of protection of such vaccines. Our results showed that intranasal immunization with formalin-killed whole cells of the LAC-4 strain elicited mucosal and systemic antigen-specific immune responses, and protected mice against lethal intranasal or intraperitoneal challenges. Compared to naïve mice, immunized mice had significantly fewer bacteria in their lungs, and the pathogen was barely detectable in blood and spleens at 24h post challenge, indicating the ability of immunized mice to control extrapulmonary dissemination of the pathogen. Mechanistic studies using gene-deficient mice, neutropenic mice, or passive immunization showed that B cells and neutrophils, but not FcRγ, played crucial roles in the protection against respiratory A. baumannii challenge of intranasally immunized mice whereas passive transfer of hyperimmune sera only prolonged the survival time of challenged mice by 48 h. These results provide immunological insights for the rational design of novel mucosal vaccines to protect against respiratory A. baumannii infection and demonstrate the feasibility to develop such vaccines.
Human Health Therapeutics, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada.
Rhonda
R
KuoLee
Human Health Therapeutics, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada.
Greg
G
Harris
Department of Chemistry, Brock University, St. Catharines, ON L2S 3A1, Canada.
Hongbin
H
Yan
Department of Biological Sciences, California State University, Los Angeles, Los Angeles, CA 90032, USA.
H Howard
HH
Xu
Human Health Therapeutics, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada.
Wayne J
WJ
Conlan
Human Health Therapeutics, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada.
Girishchandra B
GB
Patel
Human Health Therapeutics, National Research Council Canada, 100 Sussex Drive, Ottawa, Ontario K1A 0R6, Canada; Department of Biology, Brock University, St. Catharines, Ontario L2S 3A1, Canada. Electronic address: wangxue.chen@nrc.gc.ca.
Wangxue
W
Chen
D000151:Acinetobacter Infections / Q000276:immunology / Q000517:prevention & control*; D040981:Acinetobacter baumannii / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D058491:Bacterial Load; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000276:immunology*; D001769:Blood / Q000382:microbiology; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007114:Immunization / Q000379:methods*; D007116:Immunization, Passive; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000517:prevention & control*; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis
D001428:Bacterial Vaccines
Acinetobacter baumannii; B cells; Mice; Mucosal immunization; Neutrophils; Pneumonia