RESUMO
Immunomodulation enhances parasite fitness by reducing inflammation-induced morbidity in the mammalian host, as well as by attenuating parasite-targeting immune responses. Using a whole proteome differential screening method, we identified Schistosoma japonicum Helminth Defense Molecule (SjHDM-1) as a target of antibodies expressed by S. japonicum resistant, but not susceptible, individuals. In a longitudinal cohort study (N=644) conducted in a S. japonicum endemic region of the Philippines, antibody levels to SjHDM-1 did not predict resistance to reinfection but were associated with increased measures of inflammation. Individuals with high levels of anti-SjHDM-1 IgG had higher levels of C-reactive protein compared to individuals with low anti-SjHDM-1. High anti-SjHDM-1 IgG responses were also associated with reduced biomarkers of nutritional status (albumin), as well as decreased anthropometric measures of nutritional status (WAZ and HAZ) and increased measures of hepatomegaly. Our results suggest that anti-SjHDM-1 responses inhibit the immunomodulatory function of SjHDM-1, resulting in increased morbidity.
RESUMO
BACKGROUND: Schistosomiasis japonica is a zoonosis and presents significant public health problems in China and the Philippines. Vaccines targeting domestic animals constitute attractive control measures. METHODS: We conducted three vaccine trials to evaluate the protective efficacy of recombinant full-length paramyosin (rSj97) in water buffalo. Animals were immunized with 3 doses of rSj97 adjuvanted with ISA206 at 250µg/dose or 500µg/dose at 4wk intervals before challenge with 1000 Schistosoma japonicum cercariae. The primary outcome was worm burden assessed by portal perfusion 8-10weeks post challenge. Safety measures included weight, temperature, body condition score, hemogram and routine assays for hepatic and renal function. RESULTS: The three-dose regimen was well tolerated in all three trials. In the first trial, vaccinated buffalo had 51.5% lower worm burden post challenge compared to controls. In the second trial, buffalo immunized with 500µg/dose of rSj97 had 57.8% lower worm burden compared to controls (p=0.026). A similar but not significant reduction (60.9%) was observed with animals administered with 250ug rSj97/dose. In the third trial, buffalo immunized with a 500µg/dose of rSj97 had 57.8% lower worm burden compared to controls (p=0.014). CONCLUSIONS: These findings indicated that rSj97 is a safe and promising vaccine candidate for schistosomiasis japonica in water buffalo.