An oral vaccine based on U-Omp19 induces protection against B. abortus mucosal challenge by inducing an adaptive IL-17 immune response in mice

K.A. PASQUEVICH, A. E. IBAÑEZ, L. M. CORIA, C. GARCÍA SAMARTINO, S.M. ESTEIN, A.ZWERDLING, P. BARRIONUEVO, F. S. OLIVEIRA, J.BORKOWSKI¶, H. WARZECHA¶, S. C. OLIVEIRA, GUILLERMO H. GIAMBARTOLOMEI, J. CASSATARO.

PLOS ONE

PUBLIC LIBRARY SCIENCE

Año: 2011 vol. 6 p. 1 - 13

1932-6203

As Brucella infections occur mainly through mucosal surfaces, the development of mucosal administered vaccines could beradical for the control of brucellosis. In this work we evaluated the potential of Brucella abortus 19 kDa outer membraneprotein (U-Omp19) as an edible subunit vaccine against brucellosis. We investigated the protective immune responseelicited against oral B. abortus infection after vaccination of mice with leaves from transgenic plants expressing U-Omp19; orwith plant-made or E. coli-made purified U-Omp19. All tested U-Omp19 formulations induced protection against Brucellawhen orally administered without the need of adjuvants. U-Omp19 also induced protection against a systemic challengewhen parenterally administered. This built-in adjuvant ability of U-Omp19 was independent of TLR4 and could be explainedat least in part by its capability to activate dendritic cells in vivo. While unadjuvanted U-Omp19 intraperitoneallyadministered induced a specific Th1 response, following U-Omp19 oral delivery a mixed specific Th1-Th17 response wasinduced. 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 beenexplored. In this study, we determined that if IL-17A was neutralized in vivo during the challenge period, the mucosal UOmp19vaccine did not confer mucosal protection. On the contrary, IL-17A neutralization during the infection did notinfluence at all the subsistence and growth of this bacterium in PBS-immunized mice. All together, our results indicate thatan oral unadjuvanted vaccine based on U-Omp19 induces protection against a mucosal challenge with Brucella abortus byinducing an adaptive IL-17 immune response. They also indicate different and important new aspects i) IL-17 does notcontribute to reduce the bacterial burden in non vaccinated mice and ii) IL-17 plays a central role in vaccine mediated anti-Brucella mucosal immunity.