SORDELLI Daniel Oscar
congresos y reuniones científicas
Vaccination with a Staphylococcus aureus capsular polysaccharide (CP5/CP8) conjugate vaccine reduces the severity of infection in a rat model of osteomyelitis.
LATTAR SM; NOTO LLANA M; BUZZOLA FR; DENOEL P; GERMAIN S; LEE JC; SORDELLI DO
Simposio; International Symposium on Staphylococcus and staphylococcal infections ISSSI; 2010
The 2010 ISSSI Organising Committee
Implantation of prosthetic joints is associated with a definite risk of bacterial infections. Staphylococcus aureus is one of the most prevalent and difficult-to-eradicate pathogen that causes prosthetic device-associated infections. This study was conducted to evaluate the potential protective efficacy of a capsule (CP) conjugate vaccine in a rat model of experimental S. aureus osteomyelitis. Wistar rats were vaccinated with 10 µg of a CP8-conjugate by the subcutaneous route, and booster doses were given weekly for three weeks. Control rats were injected with placebo. One week after the last immunization, the rats were challenged by the intratibial route with 1x106 CFU S. aureus strain HU-92a suspended in fibrin glue (Tissucol, a tissue sealant). At 14 weeks after bacterial challenge, the rats were euthanized, and the left (infected) and right (control, non-infected) tibias were removed. A morphometric evaluation (Osteomyelitic Index, OI) of the tibias was performed to assess the severity of bone infection. The infected segment of each tibia was excised and homogenized, and the CFU determined by quantitative plate counts. Overall, there was a significant correlation between the OI and the log CFU numbers (r=0.97, p<0.01). The bacterial load (log CFU±SEM/tibia) and the OI were significantly reduced by vaccination with the CP8 conjugate compared with control rats. Rats given the CP8 vaccine had a bacterial load of 4.05±0.26 (n=7), whereas the bacterial load in control rats was 4.94±0.20 (n=10) (p=0.0147). OI medians (range) were 0.30 (0.12-1.00) (n=7) for CP8-vaccinated rats and 1.40 (0.80-7.40) (n=10) for control rats (p=0.0021). In a therapeutic approach, rats were challenged with S. aureus and then vaccinated three weeks later. Booster doses of the vaccine were given weekly for three weeks thereafter. Eight weeks after the third booster injection, the rats were euthanized and evaluated. Rats given the CP8 vaccine had a bacterial load of 3.45±0.25 (n=13), whereas the bacterial load in control animals was 4.97±0.21 (n=6) (p=0.0014). OI medians (range) were 0.40 (0.00-1.00) (n=13) for CP8-vaccinated rats and 1.05 (0.20-1.80) (n=6) for control rats (p=0.0107). Another series of experiments were performed using a CP5-conjugate vaccine. Control rats were immunized with PBS or a Streptococcus pneumoniae (Stpn)-conjugate. Vaccination with the CP5 conjugate induced also induced a significant reduction in the CFU counts and OI. The magnitude of the differences was less but still significant when vaccinated rats were compared with those vaccinated with the Stpn conjugate, indicating that the conjugated protein may have a stimulatory effect on effectors of the innate response of the host to S. aureus. Taken together, our results suggest that vaccination of rats using a CP conjugate vaccine reduces the severity of the experimentally induced bone infection. Further experiments are needed to assess the usefulness of the conjugate vaccine in individuals at risk of prosthetic device-associated infections.