Studies on a new candidate vaccine for Rhodococcus equi infections in foals

Rhodococcus (R.) equi is a facultative intracellular pathogen that causes severe pyogranulomatous pneumonia in foals up to 5 months of age. Despite the great need for a prophylactic measure against this devastating disease, no commercial vaccine is available. Today only long-term and cumbersome antibiotic treatment is available to treat the disease. Previously we reported that genes involved in cholesterol catabolism are promising targets for the development of a live-attenuated vaccine against R. equi infections. R. equi strain RG2837, a Delta ipdABipdAB2 double gene deletion mutant was impaired in growth on the cholesterol catabolic pathway intermediate 5-hydroxy-methylhexahydro-indanone-propionate. In addition, mutant strain RG2837 appeared hampered for macrophage survival and could be safelyold foals, no vaccine related abnormalities were observed, indicating that the vaccine is safe. These promising results on a candidate vaccine against R. evil warrant further studies under field conditions. administered intra-tracheally to foals at a dose at which the parent wild type strain induced pneumonia (Van der Geize et al., 2011). Subsequently, strain RG2837 was further tested for safety and efficacy in foals. One-week-old foals, vaccinated once or twice orally and challenged intra-tracheally 3 weeks later, appeared inconsistently protected against intra-tracheal challenge with virulent R. equi. However, a clear indirect correlation between protection and post-vaccination VapA serum antibody titres >= 5.0 log(2) was found which facilitated subsequent experiments, to optimize the vaccination schedule, vaccination route and vaccine composition. It was found that rectal vaccination of 5-month-old foals (in contrast to oral vaccination) induced higher and more consistent protective responses (i.e. VapA serum antibody titres >= 5.0 log(2)) in a shorter period of time. Therefore this approach was also tested in target-age animals. One-week-old foals vaccinated rectally on two consecutive days (>= 10(9) CPU per dose) were significantly protected against intra-tracheal challenge 3 weeks later. After administration of 2x10(10) CFU by the oral route or 1x10(12) CFU by the rectal route to one-week-old foals, no vaccine related abnormalities were observed, indicating that the vaccine is safe. These promising results on a candidate vaccine against R. evil warrant further studies under field conditions