Cargando…
A Mucosal Subunit Vaccine Protects against Lethal Respiratory Infection with Francisella tularensis LVS
Francisella tularensis (FT) is a highly virulent pathogen for humans and other mammals. Severe morbidity and mortality is associated with respiratory FT infection and there are concerns about intentional dissemination of this organism. Therefore, FT has been designated a category A biothreat agent a...
Autores principales: | , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508931/ https://www.ncbi.nlm.nih.gov/pubmed/23209745 http://dx.doi.org/10.1371/journal.pone.0050460 |
_version_ | 1782251257413500928 |
---|---|
author | Ashtekar, Amit R. Katz, Jannet Xu, Qingan Michalek, Suzanne M. |
author_facet | Ashtekar, Amit R. Katz, Jannet Xu, Qingan Michalek, Suzanne M. |
author_sort | Ashtekar, Amit R. |
collection | PubMed |
description | Francisella tularensis (FT) is a highly virulent pathogen for humans and other mammals. Severe morbidity and mortality is associated with respiratory FT infection and there are concerns about intentional dissemination of this organism. Therefore, FT has been designated a category A biothreat agent and there is a growing interest in the development of a protective vaccine. In the present study, we determine the protective potential of a subunit vaccine comprised of the FT heat shock protein DnaK and surface lipoprotein Tul4 against respiratory infection with the live vaccine strain (LVS) of FT in mice. First, we establish an optimal intranasal immunization regimen in C57BL/6 mice using recombinant DnaK or Tul4 together with the adjuvant GPI-0100. The individual immunization regimens induced robust salivary IgA, and vaginal and bronchoalveolar IgA and IgG antigen-specific antibodies. Serum IgG1 and IgG2c antibody responses were also induced, indicative of a mixed type 2 and type 1 response, respectively. Next, we show that immunization with DnaK and Tul4 induces mucosal and systemic antibody responses that are comparable to that seen following immunization with each antigen alone. This immunization regimen also induced IFN-γ, IL-10 and IL-17A production by splenic CD4(+) T cells in an antigen-specific manner. Importantly, over 80% of the mice immunized with DnaK and Tul4, but not with each antigen alone, were protected against a lethal respiratory challenge with FT LVS. Protection correlated with reduced bacterial burden in the lung, liver and spleen of mice. This study demonstrates the potential of DnaK and Tul4 as protective antigens and lends support to the notion of combining distinct, immunodominant antigens into an effective multivalent tularemia vaccine. |
format | Online Article Text |
id | pubmed-3508931 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35089312012-12-03 A Mucosal Subunit Vaccine Protects against Lethal Respiratory Infection with Francisella tularensis LVS Ashtekar, Amit R. Katz, Jannet Xu, Qingan Michalek, Suzanne M. PLoS One Research Article Francisella tularensis (FT) is a highly virulent pathogen for humans and other mammals. Severe morbidity and mortality is associated with respiratory FT infection and there are concerns about intentional dissemination of this organism. Therefore, FT has been designated a category A biothreat agent and there is a growing interest in the development of a protective vaccine. In the present study, we determine the protective potential of a subunit vaccine comprised of the FT heat shock protein DnaK and surface lipoprotein Tul4 against respiratory infection with the live vaccine strain (LVS) of FT in mice. First, we establish an optimal intranasal immunization regimen in C57BL/6 mice using recombinant DnaK or Tul4 together with the adjuvant GPI-0100. The individual immunization regimens induced robust salivary IgA, and vaginal and bronchoalveolar IgA and IgG antigen-specific antibodies. Serum IgG1 and IgG2c antibody responses were also induced, indicative of a mixed type 2 and type 1 response, respectively. Next, we show that immunization with DnaK and Tul4 induces mucosal and systemic antibody responses that are comparable to that seen following immunization with each antigen alone. This immunization regimen also induced IFN-γ, IL-10 and IL-17A production by splenic CD4(+) T cells in an antigen-specific manner. Importantly, over 80% of the mice immunized with DnaK and Tul4, but not with each antigen alone, were protected against a lethal respiratory challenge with FT LVS. Protection correlated with reduced bacterial burden in the lung, liver and spleen of mice. This study demonstrates the potential of DnaK and Tul4 as protective antigens and lends support to the notion of combining distinct, immunodominant antigens into an effective multivalent tularemia vaccine. Public Library of Science 2012-11-28 /pmc/articles/PMC3508931/ /pubmed/23209745 http://dx.doi.org/10.1371/journal.pone.0050460 Text en © 2012 Ashtekar et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Ashtekar, Amit R. Katz, Jannet Xu, Qingan Michalek, Suzanne M. A Mucosal Subunit Vaccine Protects against Lethal Respiratory Infection with Francisella tularensis LVS |
title | A Mucosal Subunit Vaccine Protects against Lethal Respiratory Infection with Francisella tularensis LVS |
title_full | A Mucosal Subunit Vaccine Protects against Lethal Respiratory Infection with Francisella tularensis LVS |
title_fullStr | A Mucosal Subunit Vaccine Protects against Lethal Respiratory Infection with Francisella tularensis LVS |
title_full_unstemmed | A Mucosal Subunit Vaccine Protects against Lethal Respiratory Infection with Francisella tularensis LVS |
title_short | A Mucosal Subunit Vaccine Protects against Lethal Respiratory Infection with Francisella tularensis LVS |
title_sort | mucosal subunit vaccine protects against lethal respiratory infection with francisella tularensis lvs |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3508931/ https://www.ncbi.nlm.nih.gov/pubmed/23209745 http://dx.doi.org/10.1371/journal.pone.0050460 |
work_keys_str_mv | AT ashtekaramitr amucosalsubunitvaccineprotectsagainstlethalrespiratoryinfectionwithfrancisellatularensislvs AT katzjannet amucosalsubunitvaccineprotectsagainstlethalrespiratoryinfectionwithfrancisellatularensislvs AT xuqingan amucosalsubunitvaccineprotectsagainstlethalrespiratoryinfectionwithfrancisellatularensislvs AT michaleksuzannem amucosalsubunitvaccineprotectsagainstlethalrespiratoryinfectionwithfrancisellatularensislvs AT ashtekaramitr mucosalsubunitvaccineprotectsagainstlethalrespiratoryinfectionwithfrancisellatularensislvs AT katzjannet mucosalsubunitvaccineprotectsagainstlethalrespiratoryinfectionwithfrancisellatularensislvs AT xuqingan mucosalsubunitvaccineprotectsagainstlethalrespiratoryinfectionwithfrancisellatularensislvs AT michaleksuzannem mucosalsubunitvaccineprotectsagainstlethalrespiratoryinfectionwithfrancisellatularensislvs |