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Conventional vaccines to prevent the pneumonia caused by  Rhodococcus equi  have not been successful. We have recently demonstrated that immunization with  Salmonella enterica  Typhimurium expressing the VapA antigen protects mice against  R. equi  infection. We now report that oral vaccination of mice with this recombinant strain results in high and persistent fecal levels of antigen-specific IgA, and specific proliferation of the spleen cells of immunized mice in response to the  in vitro  stimulation with  R. equi  antigen. After  in vitro  stimulation, spleen cells of immunized mice produce high levels of Th1 cytokines and show a prominent mRNA expression of the Th1 transcription factor T-bet, in detriment of the Th2 transcription factor GATA-3. Following  R. equi  challenge, a high H 2 O 2 , NO, IL-12, and IFN-γ content is detected in the organs of immunized mice. On the other hand, TNF-α and IL-4 levels are markedly lower in the organs of vaccinated mice, compared with the non-vaccinated ones. The IL-10 content and the mRNA transcription level of TGF-β are also higher in the organs of immunized mice. A greater incidence of CD4 +  and CD8 +  T cells and B lymphocytes is verified in vaccinated mice. However, there is no difference between vaccinated and non-vaccinated mice in terms of the frequency of CD4 + CD25 + Foxp3 +  T cells. Finally, we show that the vaccination confers a long-term protection against  R. equi  infection. Altogether, these data indicate that the oral vaccination of mice with  S. enterica  Typhimurium expressing VapA induces specific and long-lasting humoral and cellular responses against the pathogen, which are appropriately regulated and allow tissue integrity after challenge.

Vaccination of Mice with Salmonella Expressing VapA: Mucosal and Systemic Th1 Responses Provide Protection against Rhodococcus equi Infection