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PrtA immunization fails to protect against pulmonary and invasive infection by Streptococcus pneumoniae

BACKGROUND: Streptococcus pneumoniae is a respiratory pathogen causing severe lung infection that may lead to complications such as bacteremia. Current polysaccharide vaccines have limited serotype coverage and therefore cannot provide maximal and long-term protection. Global efforts are being made...

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Autores principales: Hsu, Chen-Fang, Hsiao, Chen-Hao, Tseng, Shun-Fu, Chen, Jian-Ru, Liao, Yu-Jou, Chen, Sy-Jou, Lin, Chin-Sheng, Sytwu, Huey-Kang, Chuang, Yi-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157060/
https://www.ncbi.nlm.nih.gov/pubmed/30253765
http://dx.doi.org/10.1186/s12931-018-0895-8
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author Hsu, Chen-Fang
Hsiao, Chen-Hao
Tseng, Shun-Fu
Chen, Jian-Ru
Liao, Yu-Jou
Chen, Sy-Jou
Lin, Chin-Sheng
Sytwu, Huey-Kang
Chuang, Yi-Ping
author_facet Hsu, Chen-Fang
Hsiao, Chen-Hao
Tseng, Shun-Fu
Chen, Jian-Ru
Liao, Yu-Jou
Chen, Sy-Jou
Lin, Chin-Sheng
Sytwu, Huey-Kang
Chuang, Yi-Ping
author_sort Hsu, Chen-Fang
collection PubMed
description BACKGROUND: Streptococcus pneumoniae is a respiratory pathogen causing severe lung infection that may lead to complications such as bacteremia. Current polysaccharide vaccines have limited serotype coverage and therefore cannot provide maximal and long-term protection. Global efforts are being made to develop a conserved protein vaccine candidate. PrtA, a pneumococcal surface protein, was identified by screening a pneumococcal genomic expression library using convalescent patient serum. The prtA gene is prevalent and conserved among S. pneumoniae strains. Its protective efficacy, however, has not been described. Mucosal immunization could sensitize both local and systemic immunity, which would be an ideal scenario for preventing S. pneumoniae infection. METHODS: We immunized BALB/c mice intranasally with a combination of a PrtA fragment (amino acids 144–1041) and Th17 potentiated adjuvant, curdlan. We then measured the T-cell and antibody responses. The protective efficacy conferred to the immunized mice was further evaluated using a murine model of acute pneumococcal pneumonia and pneumococcal bacteremia. RESULTS: There was a profound antigen-specific IL-17A and IFN-γ response in PrtA-immunized mice compared with that of adjuvant control group. Even though PrtA-specific IgG and IgA titer in sera was elevated in immunized mice, only a moderate IgA response was observed in the bronchoalveolar lavage fluid. The PrtA-immunized antisera facilitated the activated murine macrophage, RAW264.7, to opsonophagocytose S. pneumoniae D39 strain; however, PrtA-specific immunoglobulins bound to pneumococcal surfaces with a limited potency. Finally, PrtA-induced immune reactions failed to protect mice against S. pneumoniae-induced acute pneumonia and bacterial propagation through the blood. CONCLUSIONS: Immunization with recombinant PrtA combined with curdlan produced antigen-specific antibodies and elicited IL-17A response. However, it failed to protect the mice against S. pneumoniae-induced infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0895-8) contains supplementary material, which is available to authorized users.
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spelling pubmed-61570602018-09-27 PrtA immunization fails to protect against pulmonary and invasive infection by Streptococcus pneumoniae Hsu, Chen-Fang Hsiao, Chen-Hao Tseng, Shun-Fu Chen, Jian-Ru Liao, Yu-Jou Chen, Sy-Jou Lin, Chin-Sheng Sytwu, Huey-Kang Chuang, Yi-Ping Respir Res Research BACKGROUND: Streptococcus pneumoniae is a respiratory pathogen causing severe lung infection that may lead to complications such as bacteremia. Current polysaccharide vaccines have limited serotype coverage and therefore cannot provide maximal and long-term protection. Global efforts are being made to develop a conserved protein vaccine candidate. PrtA, a pneumococcal surface protein, was identified by screening a pneumococcal genomic expression library using convalescent patient serum. The prtA gene is prevalent and conserved among S. pneumoniae strains. Its protective efficacy, however, has not been described. Mucosal immunization could sensitize both local and systemic immunity, which would be an ideal scenario for preventing S. pneumoniae infection. METHODS: We immunized BALB/c mice intranasally with a combination of a PrtA fragment (amino acids 144–1041) and Th17 potentiated adjuvant, curdlan. We then measured the T-cell and antibody responses. The protective efficacy conferred to the immunized mice was further evaluated using a murine model of acute pneumococcal pneumonia and pneumococcal bacteremia. RESULTS: There was a profound antigen-specific IL-17A and IFN-γ response in PrtA-immunized mice compared with that of adjuvant control group. Even though PrtA-specific IgG and IgA titer in sera was elevated in immunized mice, only a moderate IgA response was observed in the bronchoalveolar lavage fluid. The PrtA-immunized antisera facilitated the activated murine macrophage, RAW264.7, to opsonophagocytose S. pneumoniae D39 strain; however, PrtA-specific immunoglobulins bound to pneumococcal surfaces with a limited potency. Finally, PrtA-induced immune reactions failed to protect mice against S. pneumoniae-induced acute pneumonia and bacterial propagation through the blood. CONCLUSIONS: Immunization with recombinant PrtA combined with curdlan produced antigen-specific antibodies and elicited IL-17A response. However, it failed to protect the mice against S. pneumoniae-induced infection. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12931-018-0895-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-09-25 2018 /pmc/articles/PMC6157060/ /pubmed/30253765 http://dx.doi.org/10.1186/s12931-018-0895-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Hsu, Chen-Fang
Hsiao, Chen-Hao
Tseng, Shun-Fu
Chen, Jian-Ru
Liao, Yu-Jou
Chen, Sy-Jou
Lin, Chin-Sheng
Sytwu, Huey-Kang
Chuang, Yi-Ping
PrtA immunization fails to protect against pulmonary and invasive infection by Streptococcus pneumoniae
title PrtA immunization fails to protect against pulmonary and invasive infection by Streptococcus pneumoniae
title_full PrtA immunization fails to protect against pulmonary and invasive infection by Streptococcus pneumoniae
title_fullStr PrtA immunization fails to protect against pulmonary and invasive infection by Streptococcus pneumoniae
title_full_unstemmed PrtA immunization fails to protect against pulmonary and invasive infection by Streptococcus pneumoniae
title_short PrtA immunization fails to protect against pulmonary and invasive infection by Streptococcus pneumoniae
title_sort prta immunization fails to protect against pulmonary and invasive infection by streptococcus pneumoniae
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6157060/
https://www.ncbi.nlm.nih.gov/pubmed/30253765
http://dx.doi.org/10.1186/s12931-018-0895-8
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