INVESTIGADORES
SORDELLI Daniel Oscar
congresos y reuniones científicas
Título:
Vaccination with a Staphylococcus aureus capsular polysaccharide (CP5/CP8) conjugate vaccine reduces the severity of infection in a rat model of osteomyelitis
Autor/es:
LATTAR SM; NOTO LLANA M; BUZZOLA FR; DENOEL P; GERMAIN S; LEE JC; SORDELLI DO
Lugar:
Bath
Reunión:
Congreso; International Symposium on Staphylococcus and Staphylococcal Infections (ISSSI); 2009
Institución organizadora:
ISSSI
Resumen:
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.