| Rhodococcus equi remains one of the most important pathogens early in life in horses, yet vaccines against rhodococcal pneumonia have not been successful so far. Since immunocompetent adult horses are not susceptible to R. equi disease, in this study our goals were first, to understand the protective immune response against R. equi in adult horses and second, to develop a vaccine that induces that protective phenotype in the foal.; To characterize the correlates of protection, twelve adult horses were challenged with virulent R. equi. Bronchoalveolar lavage fluid (BALF) cells stimulated with either R. equi or the vaccine candidate VapA resulted in significant proliferation and a significant increase in IFN-γ expression by day 7 post-challenge. Anamnestic increases in all examined IgG antibody isotypes (IgGa, IgGb, IgG(T)) binding R. equi and VapA were detected post-challenge. Anti-VapA IgGb and anti-R. equi IgGa and IgGb antibodies, the equine IgG isotypes that preferentially opsonize and fix complement, were dramatically enhanced and were the predominant isotypes post-challenge. The antigen-specific proliferation of BALF cells, IFN-γ expression by these cells, and the anamnestic increases in opsonizing IgG isotypes are consistent with stimulation of a memory response in immune adult horses and represent correlates for vaccine development in foals.; We developed a DNA vaccine expressing the vapA gene (pVR1055vapA) that induced VapA-specific immune responses in adult ponies. To determine if pVR1055vapA generated VapA-specific primary immune responses, two-week old foals were vaccinated (day 1) by intranasal and intradermal routes with either pVR1055vapA or the negative control pVR1055vapA_rev. All foals were DNA boosted (day 14) and protein boosted (day 30) with either rVapA (VR1055vapA-vaccinates) or rCAT (control group). At day 45, no antigen-specific antibody responses were detected in the control group. However, VapA-specific IgGb, IgGa and IgM were detected in sera of three foals of the VR1055vapAvaccinated group. Two of these animals also had VapA-specific IgG in BALF. These results indicate that although the DNA vaccine reported needs to be improved, it stimulates antibody isotypes associated with protection and therefore constitutes a promising vaccination system against R. equi infection. |
