Yeast-based approaches have opened unique windows of opportunities to decipher fundamental aspects of biology and, more recently, these microorganisms have also found a special place in the vaccinology field. Yeasts are easily targeted by immune surveillance mechanisms due to the presence of conserved cell wall carbohydrates that are absent in hosts including mammals and poultry. For this reason, whole yeast-based vaccines do not require adjuvants. Besides, yeast cell wall components are able to induce Th1, Th17 and cytotoxic T-cell responses, surpassing the antibody-biased responses elicited by conventional adjuvanted-vaccines. These particularities, combined with the versatility of yeasts as heterologous protein expression systems, highlight the potential of these organisms as vaccine platforms to fight animal diseases. As a proof of concept, we took advantage of the yeast-surface display (YSD) technology to produce a recombinant strain of Saccharomyces cerevisiae (Sce) expressing the outer membrane protein A (OmpA) of Escherichia coli (herein, Sce-OmpA). E. coli is an important cause of bovine mastitis and OmpA has been reported as a potential candidate antigen for vaccine development. Then, we evaluated the in vitro response of PBMC from OmpA-immunized cloned cows upon stimulation with heat-inactivated Sce-OmpA. A higher release of INFγ and IL-17 was observed in cells exposed to Sce-OmpA, compared to empty Sce, heat-killed E. coli or OmpA recombinant protein. In addition, antigen delivery by Sce enhanced the activation and proliferation of CD4+ and CD8+ T-cells. Interestingly, the levels of response varied in an individual-dependent way, in spite of the homogeneous genetic background of PBMC donor animals. This observation demonstrates that the T-cell response to the tested platform is not strictly determined on a genetic basis and might be shaped by other factors such as previous exposure to environmental microorganisms and/or antigens. In summary, these results suggest that the delivery of bacterial antigens by heat-inactivated yeast can boost and shape bovine T-cell responses, paving the way for the development of non-toxic, cost-effective and adjuvant-free yeast-based vaccines for cattle. We are currently evaluating the safety and efficiency of this platform in vivo.