An Oral Vaccine Based on U-Omp19 Induces Protection against B. abortus Mucosal Challenge by Inducing an Adaptive IL-17 Immune Response in Mice

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.

TLR2 and TLR4 signaling pathways are required for recombinant Brucella abortus BCSP31-induced cytokine production, functional upregulation of mouse macrophages, and the Th1 immune response in vivo and in vitro

“…80 Similarly, unlipidated outer membrane protein 19 of B. abortus induces a Th17 immune response and confers 1.12 log units of protection against B. abortus 2308 infection in C57BL/6 mice that is independent of TLR4. 81 Our result indicates that rBCSP31 vaccination provides a similar level of protection (1.10 log units of protection) against B. abortus to these single antigens expressed in E. coli. Our results showed that vaccination with rBCSP31 provided a higher level of protection against B. abortus infection in C57BL/ 6micecomparedwithTLR2 2/2 andTLR4 2/2 mice,demonstrating that TLR2 and TLR4 function as important molecules in the rBCSP31-triggered protective immune response.…”

Oral immunization of mice with Omp31-loaded <em>N</em>-trimethyl chitosan nanoparticles induces high protection against <em>Brucella melitensis</em> infection

“…We showed that oral administration of TMC/ Omp31 NPs induces a significant cellular-mixed Th1-Th17 immune response that is in accordance with the observations by Pasquevich et al 36 and Abkar et al 44 that had shown that oral administration of another antigen (plant-expressed Omp19) and TMC/Omp19 elicits a significant cellular-mixed Th1-Th17 immune response. In a study conducted by Abkar et al, oral vaccination with TMC/Omp19 induced immune responses and a high level of protection against systemic infection.…”

“…Currently, licensed human or animal vaccines are generally administered by the parenteral route, but then again, oral vaccines have many advantages compared to systemic injections. 36 As the Brucella bacterium often enters the body via contaminated food and/or water, mucosal immunity can act as a first barrier against the infection before it reaches the bloodstream. 37 Hence, one of the goals of this study was the elicitation of anti-Brucella IgA in mucosal sites.…”

“…It has been indicated that an IL-4-dependent Th2 response does not develop or play a negative role during the Brucella pathogenesis, whereas pathogen-specific Th17 cells may boost or work synergistically with Th1 cells for high protection against Brucella infection. 36,45 Hence, high levels of Th17 immune responses in oral administration can be one of the reasons behind the high level of protection obtained against B. melitensis challenges compared to the protection level attained in ip immunization.…”

Evaluation of Immunogenicity of Dna Vaccine Coding Outer Membrane Protein 31 (Omp31) of Brucella Melitensis in Mice.

“…Subunit recombinant protein vaccines are considered promising vaccines because they are effective, less biohazardous, well-defined, non-infectious and persuade long-actingprotection [5,6].Furthermore, it is essential to ISSN: 2320-5407 Int. J. Adv.…”