TY  - JOUR
A1  - Roier, Sandro
A1  - Leitner, Deborah R.
A1  - Iwashkiw, Jeremy
A1  - Schild-Prüfert, Kristina
A1  - Feldman, Mario F.
A1  - Krohne, Georg
A1  - Reidl, Joachim
A1  - Schild, Stefan
T1  - Intranasal Immunization with Nontypeable Haemophilus influenzae Outer Membrane Vesicles Induces Cross-Protective Immunity in Mice
JF  - PLoS One
N2  - Haemophilus influenzae is a Gram-negative human-restricted bacterium that can act as a commensal and a pathogen of the respiratory tract. Especially nontypeable H. influenzae (NTHi) is a major threat to public health and is responsible for several infectious diseases in humans, such as pneumonia, sinusitis, and otitis media. Additionally, NTHi strains are highly associated with exacerbations in patients suffering from chronic obstructive pulmonary disease. Currently, there is no licensed vaccine against NTHi commercially available. Thus, this study investigated the utilization of outer membrane vesicles (OMVs) as a potential vaccine candidate against NTHi infections. We analyzed the immunogenic and protective properties of OMVs derived from various NTHi strains by means of nasopharyngeal immunization and colonization studies with BALB/c mice. The results presented herein demonstrate that an intranasal immunization with NTHi OMVs results in a robust and complex humoral and mucosal immune response. Immunoprecipitation revealed the most important immunogenic proteins, such as the heme utilization protein, protective surface antigen D15, heme binding protein A, and the outer membrane proteins P1, P2, P5 and P6. The induced immune response conferred not only protection against colonization with a homologous NTHi strain, which served as an OMV donor for the immunization mixtures, but also against a heterologous NTHi strain, whose OMVs were not part of the immunization mixtures. These findings indicate that OMVs derived from NTHi strains have a high potential to act as a vaccine against NTHi infections.
KW  - conjugate
KW  - obstructive pulmonary disease
KW  - vaccine
KW  - vibrio cholerae
KW  - detoxified lipooligosaccharide
KW  - nasopharyngeal colonization
KW  - functional characterization
KW  - growing escherichia coli
KW  - DNA-binding vesicles
KW  - otitis media
KW  - hemophilus influenzae
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135201
VL  - 7
IS  - 8
ER  - 
TY  - JOUR
A1  - Kurabi, Arwa
A1  - Pak, Kwang K.
A1  - Bernhardt, Marlen
A1  - Baird, Andrew
A1  - Ryan, Allen F.
T1  - Discovery of a Biological Mechanism of Active Transport through the Tympanic Membrane to the Middle Ear
JF  - Scientific Reports
N2  - Otitis media (OM) is a common pediatric disease for which systemic antibiotics are often prescribed. While local treatment would avoid the systemic treatment side-effects, the tympanic membrane (TM) represents an impenetrable barrier unless surgically breached. We hypothesized that the TM might harbor innate biological mechanisms that could mediate trans-TM transport. We used two M13-bacteriophage display biopanning strategies to search for mediators of trans-TM transport. First, aliquots of linear phage library displaying 10\(^{10th}\) 12mer peptides were applied on the TM of rats with active bacterial OM. The middle ear (ME) contents were then harvested, amplified and the preparation re-applied for additional rounds. Second, the same naïve library was sequentially screened for phage exhibiting TM binding, internalization and then transit. Results revealed a novel set of peptides that transit across the TM to the ME in a time and temperature dependent manner. The peptides with highest transport capacities shared sequence similarities. Historically, the TM was viewed as an impermeable barrier. However, our studies reveal that it is possible to translocate peptide-linked small particles across the TM. This is the first comprehensive biopanning for the isolation of TM transiting peptidic ligands. The identified mechanism offers a new drug delivery platform into the ME.
KW  - biological mechanism
KW  - otitis media
KW  - tympanic membrane
KW  - active transport
KW  - middle ear
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-167741
VL  - 6
IS  - 22663
ER  -