An Oral Vaccine Based on U-Omp19 Induces Protection against B. abortus Mucosal Challenge by Inducing an Adaptive IL-17 Immune Response in Mice
Open Access
- 14 January 2011
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 6 (1), e16203
- https://doi.org/10.1371/journal.pone.0016203
Abstract
As Brucella infections occur mainly through mucosal surfaces, the development of mucosal administered vaccines could be radical for the control of brucellosis. In this work we evaluated the potential of Brucella abortus 19 kDa outer membrane protein (U-Omp19) as an edible subunit vaccine against brucellosis. We investigated the protective immune response elicited against oral B. abortus infection after vaccination of mice with leaves from transgenic plants expressing U-Omp19; or with plant-made or E. coli-made purified U-Omp19. All tested U-Omp19 formulations induced protection against Brucella when orally administered without the need of adjuvants. U-Omp19 also induced protection against a systemic challenge when parenterally administered. This built-in adjuvant ability of U-Omp19 was independent of TLR4 and could be explained at least in part by its capability to activate dendritic cells in vivo. While unadjuvanted U-Omp19 intraperitoneally administered induced a specific Th1 response, following U-Omp19 oral delivery a mixed specific Th1-Th17 response was induced. Depletion of CD4+ T cells in mice orally vaccinated with U-Omp19 resulted in a loss of the elicited protection, indicating that this cell type mediates immune protection. The role of IL-17 against Brucella infection has never been explored. In this study, we determined that if IL-17A was neutralized in vivo during the challenge period, the mucosal U-Omp19 vaccine did not confer mucosal protection. On the contrary, IL-17A neutralization during the infection did not influence at all the subsistence and growth of this bacterium in PBS-immunized mice. All together, our results indicate that an oral unadjuvanted vaccine based on U-Omp19 induces protection against a mucosal challenge with Brucella abortus by inducing an adaptive IL-17 immune response. They also indicate different and important new aspects i) IL-17 does not contribute to reduce the bacterial burden in non vaccinated mice and ii) IL-17 plays a central role in vaccine mediated anti-Brucella mucosal immunity.Keywords
This publication has 72 references indexed in Scilit:
- Interleukin-17 Is Required for T Helper 1 Cell Immunity and Host Resistance to the Intracellular Pathogen Francisella tularensisImmunity, 2009
- Nondividing but Metabolically Active Gamma-IrradiatedBrucella melitensisIs Protective against VirulentB. melitensisChallenge in MiceInfection and Immunity, 2009
- Th17 cells at the crossroads of innate and adaptive immunity against infectious diseases at the mucosaMucosal Immunology, 2009
- A novel IL-17-dependent mechanism of cross protection: Respiratory infection with mycoplasma protects against a secondary listeria infectionEuropean Journal of Immunology, 2009
- Interleukin‐17 in host defence against bacterial, mycobacterial and fungal pathogensImmunology, 2009
- IL-17A is produced by Th17, T cells and other CD4- lymphocytes during infection with Salmonella enterica serovar Enteritidis and has a mild effect in bacterial clearanceInternational Immunology, 2008
- Simian immunodeficiency virus–induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gutNature Medicine, 2008
- IL-23 and IL-17 in tuberculosisCytokine, 2008
- Improved Immunogenicity of a Vaccination Regimen Combining a DNA Vaccine Encoding Brucella melitensis Outer Membrane Protein 31 (Omp31) and Recombinant Omp31 BoostingClinical and Vaccine Immunology, 2007
- A Bile Salt Hydrolase of Brucella abortus Contributes to the Establishment of a Successful Infection through the Oral Route in MiceInfection and Immunity, 2007