Induction of immune response to the 17 kDa OMPA Burkholderia cenocepacia polypeptide and protection against pulmonary infection in mice after nasal vaccination with an OMP nanoemulsion-based vaccine.
Burkholderia cepacia complex (Bcc) are opportunistic bacteria associated with life-threatening illness in persons with cystic fibrosis. Once Bcc colonization is established, these antimicrobial-resistant and biofilm-forming bacteria are difficult to eradicate and are associated with increased rates of morbidity and mortality. At present, no vaccines are available to prevent the Bcc infection. There is currently a paucity of published information regarding the development of vaccines designed to prevent Burkholderia colonization. This work expands on the recent studies published by Bertot et al. [Infect Immun 75(6):2740-2752, 2007], where successful protective immune responses were generated in mice using a B. multivorans OMP-based vaccine. Here, we evaluate an experimental mucosal vaccine against Bcc using a novel mucosal adjuvant (nanoemulsion) and a novel B. cenocepacia-based OMP antigen. The OMP antigen derived from B. cenocepacia was mixed with either nanoemulsion or with PBS and delivered intranasally to CD-1 mice. Serum analysis showed robust IgG and mucosal secretory IgA immune responses in vaccinated versus control mice. The antibodies had cross-neutralizing activity against both B. cenocepacia and B. multivorans species. We found that immunized mice were protected against pulmonary colonization with B. cenocepacia. We have also identified that a 17 kDa OmpA-like protein highly conserved between Burkholderia and Ralstonia species as a new immunodominant epitope in mucosal immunization.
Makidon
P E
PE
Michigan Nanotechnology Institute for Medicine and Biological Sciences (MNIMBS), University of Michigan, 9220 MSRB III, 1150 W. Medical Center Dr., Ann Arbor, MI, 48109-5648, USA. pmakidon@umich.edu
Knowlton
J
J
Groom
J V
JV
Blanco
L P
LP
LiPuma
J J
JJ
Bielinska
A U
AU
Baker
J R
JR
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D057134:Antibodies, Neutralizing / Q000276:immunology; D000917:Antibody Formation; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D019121:Burkholderia Infections / Q000276:immunology / Q000517:prevention & control*; D042602:Burkholderia cepacia complex / Q000276:immunology; D003429:Cross Reactions; D004655:Emulsions / Q000494:pharmacology; D000939:Epitopes / Q000276:immunology; D005260:Female; D007111:Immunity, Cellular; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008969:Molecular Sequence Data; D012141:Respiratory Tract Infections / Q000276:immunology / Q000517:prevention & control*; D016415:Sequence Alignment; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D057134:Antibodies, Neutralizing; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D004655:Emulsions; D000939:Epitopes; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; C078167:OMPA outer membrane proteins