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Delivery of a Chlamydial Adhesin N-PmpC Subunit Vaccine to the Ocular Mucosa Using Particulate Carriers

Inić-Kanada, Aleksandra; Stojanović, Marijana; Schlacher, Simone; Stein, Elisabeth; Belij-Rammerstorfer, Sandra; Marinković, Emilija; Lukić, Ivana; Montanaro, Jacqueline; Schuerer, Nadine; Bintner, Nora; Kovačević-Jovanović, Vesna; Krnjaja, Ognjen; Mayr, Ulrike Beate; Lubitz, Werner; Barisani-Asenbauer, Talin

(Public Library Science, San Francisco, 2015)

TY  - JOUR
AU  - Inić-Kanada, Aleksandra
AU  - Stojanović, Marijana
AU  - Schlacher, Simone
AU  - Stein, Elisabeth
AU  - Belij-Rammerstorfer, Sandra
AU  - Marinković, Emilija
AU  - Lukić, Ivana
AU  - Montanaro, Jacqueline
AU  - Schuerer, Nadine
AU  - Bintner, Nora
AU  - Kovačević-Jovanović, Vesna
AU  - Krnjaja, Ognjen
AU  - Mayr, Ulrike Beate
AU  - Lubitz, Werner
AU  - Barisani-Asenbauer, Talin
PY  - 2015
UR  - http://intor.torlakinstitut.com/handle/123456789/434
AB  - Trachoma, caused by the intracellular bacterium Chlamydia trachomatis (Ct), remains the world's leading preventable infectious cause of blindness. Recent attempts to develop effective vaccines rely on modified chlamydial antigen delivery platforms. As the mechanisms engaged in the pathology of the disease are not fully understood, designing a subunit vaccine specific to chlamydial antigens could improve safety for human use. We propose the delivery of chlamydia-specific antigens to the ocular mucosa using particulate carriers, bacterial ghosts (BGs). We therefore characterized humoral and cellular immune responses after conjunctival and subcutaneous immunization with a N-terminal portion (amino acid 1-893) of the chlamydial polymorphic membrane protein C (PmpC) of Ct serovar B, expressed in probiotic Escherichia coli Nissle 1917 bacterial ghosts (EcN BGs) in BALB/cmice. Three immunizations were performed at two-week intervals, and the immune responses were evaluated two weeks after the final immunization in mice. In a guinea pig model of ocular infection animals were immunized in the same manner as the mice, and protection against challenge was assessed two weeks after the last immunization. N-PmpC was successfully expressed within BGs and delivery to the ocularmucosa was well tolerated without signs of inflammation. N-PmpC- specific mucosal IgA levels in tears yielded significantly increased levels in the group immunized via the conjunctiva compared with the subcutaneously immunized mice. Immunization with N-PmpC EcN BGs via both immunization routes prompted the establishment of an N-PmpC-specific IFN gamma immune response. Immunization via the conjunctiva resulted in a decrease in intensity of the transitional inflammatory reaction in conjunctiva of challenged guinea pigs compared with subcutaneously and non-immunized animals. The delivery of the chlamydial subunit vaccine to the ocular mucosa using a particulate carrier, such as BGs, induced both humoral and cellular immune responses. Further investigations are needed to improve the immunization scheme and dosage.
PB  - Public Library Science, San Francisco
T2  - PLoS One
T1  - Delivery of a Chlamydial Adhesin N-PmpC Subunit Vaccine to the Ocular Mucosa Using Particulate Carriers
IS  - 12
VL  - 10
DO  - 10.1371/journal.pone.0144380
ER  - 
@article{
author = "Inić-Kanada, Aleksandra and Stojanović, Marijana and Schlacher, Simone and Stein, Elisabeth and Belij-Rammerstorfer, Sandra and Marinković, Emilija and Lukić, Ivana and Montanaro, Jacqueline and Schuerer, Nadine and Bintner, Nora and Kovačević-Jovanović, Vesna and Krnjaja, Ognjen and Mayr, Ulrike Beate and Lubitz, Werner and Barisani-Asenbauer, Talin",
year = "2015",
abstract = "Trachoma, caused by the intracellular bacterium Chlamydia trachomatis (Ct), remains the world's leading preventable infectious cause of blindness. Recent attempts to develop effective vaccines rely on modified chlamydial antigen delivery platforms. As the mechanisms engaged in the pathology of the disease are not fully understood, designing a subunit vaccine specific to chlamydial antigens could improve safety for human use. We propose the delivery of chlamydia-specific antigens to the ocular mucosa using particulate carriers, bacterial ghosts (BGs). We therefore characterized humoral and cellular immune responses after conjunctival and subcutaneous immunization with a N-terminal portion (amino acid 1-893) of the chlamydial polymorphic membrane protein C (PmpC) of Ct serovar B, expressed in probiotic Escherichia coli Nissle 1917 bacterial ghosts (EcN BGs) in BALB/cmice. Three immunizations were performed at two-week intervals, and the immune responses were evaluated two weeks after the final immunization in mice. In a guinea pig model of ocular infection animals were immunized in the same manner as the mice, and protection against challenge was assessed two weeks after the last immunization. N-PmpC was successfully expressed within BGs and delivery to the ocularmucosa was well tolerated without signs of inflammation. N-PmpC- specific mucosal IgA levels in tears yielded significantly increased levels in the group immunized via the conjunctiva compared with the subcutaneously immunized mice. Immunization with N-PmpC EcN BGs via both immunization routes prompted the establishment of an N-PmpC-specific IFN gamma immune response. Immunization via the conjunctiva resulted in a decrease in intensity of the transitional inflammatory reaction in conjunctiva of challenged guinea pigs compared with subcutaneously and non-immunized animals. The delivery of the chlamydial subunit vaccine to the ocular mucosa using a particulate carrier, such as BGs, induced both humoral and cellular immune responses. Further investigations are needed to improve the immunization scheme and dosage.",
publisher = "Public Library Science, San Francisco",
journal = "PLoS One",
title = "Delivery of a Chlamydial Adhesin N-PmpC Subunit Vaccine to the Ocular Mucosa Using Particulate Carriers",
number = "12",
volume = "10",
doi = "10.1371/journal.pone.0144380"
}
Inić-Kanada, A., Stojanović, M., Schlacher, S., Stein, E., Belij-Rammerstorfer, S., Marinković, E., Lukić, I., Montanaro, J., Schuerer, N., Bintner, N., Kovačević-Jovanović, V., Krnjaja, O., Mayr, U. B., Lubitz, W.,& Barisani-Asenbauer, T.. (2015). Delivery of a Chlamydial Adhesin N-PmpC Subunit Vaccine to the Ocular Mucosa Using Particulate Carriers. in PLoS One
Public Library Science, San Francisco., 10(12).
https://doi.org/10.1371/journal.pone.0144380
Inić-Kanada A, Stojanović M, Schlacher S, Stein E, Belij-Rammerstorfer S, Marinković E, Lukić I, Montanaro J, Schuerer N, Bintner N, Kovačević-Jovanović V, Krnjaja O, Mayr UB, Lubitz W, Barisani-Asenbauer T. Delivery of a Chlamydial Adhesin N-PmpC Subunit Vaccine to the Ocular Mucosa Using Particulate Carriers. in PLoS One. 2015;10(12).
doi:10.1371/journal.pone.0144380 .
Inić-Kanada, Aleksandra, Stojanović, Marijana, Schlacher, Simone, Stein, Elisabeth, Belij-Rammerstorfer, Sandra, Marinković, Emilija, Lukić, Ivana, Montanaro, Jacqueline, Schuerer, Nadine, Bintner, Nora, Kovačević-Jovanović, Vesna, Krnjaja, Ognjen, Mayr, Ulrike Beate, Lubitz, Werner, Barisani-Asenbauer, Talin, "Delivery of a Chlamydial Adhesin N-PmpC Subunit Vaccine to the Ocular Mucosa Using Particulate Carriers" in PLoS One, 10, no. 12 (2015),
https://doi.org/10.1371/journal.pone.0144380 . .
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