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.
Highlights
Mucosal surfaces are the initial sites of contact and entry for a vast majority of pathogens; the induction of protective immunity at these mucosal surfaces is usually an expected attribute in the field of development of new vaccines [1]
As lipidation is not a common posttranslational modification in plants, we first studied whether a plant-made vaccine based on unlipidated (U)-Omp19 expression would be effective against brucellosis
The protection level elicited by the plantderived U-Omp19 did not differ significantly from that elicited by the recombinant E. coli-made U-Omp19 (1.26 units of protection vs. 1.22 units of protection, P.0.05) (Table 1)
Summary
Mucosal surfaces (e.g. gastrointestinal, respiratory and urogenital tracts) are the initial sites of contact and entry for a vast majority of pathogens; the induction of protective immunity at these mucosal surfaces is usually an expected attribute in the field of development of new vaccines [1]. Mucosal-administered vaccines have the potential ability to induce humoral and cell-mediated immune responses at mucosal sites and at the systemic level, likewise [1]. This attribute of mucosal vaccines together with their needle-less, noninvasive immunization approach make them a very attractive vaccination choice. Plant-based edible vaccines are endowed with all the attractive features of mucosal vaccines along with other distinctiveness unique to plant expression systems, such as the lack of requirement of fermentation and protein purification processes, the cost-effective production because of the low energy input and the low cost of supplies and the easy vaccine transportation, preservation and delivery [2]. Edible vaccines could be suited for meat-markets-destined farm animals, as repeated injections can deteriorate the carcass quality [3]
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