Safety and immunogenicity of rSh28GST antigen in humans: phase 1 randomized clinical study of a vaccine candidate against urinary schistosomiasis.

BACKGROUND: Treatment of urinary schistosomiasis by chemotherapy remains challenging due to rapid re-infection and possibly to limited susceptibility to praziquantel treatment. Therefore, therapeutic vaccines represent an attractive alternative control strategy. The objectives of this study were to assess the safety and tolerability profile of the recombinant 28 kDa glutathione S-transferase of Schistosoma haematobium (rSh28GST) in healthy volunteers, and to determine its immunogenicity. METHODOLOGY: Volunteers randomly received 100 µg rSh28GST together with aluminium hydroxide (Alum) as adjuvant (n = 8), or Alum alone as a comparator (n = 8), twice with a 28-day interval between doses. A third dose of rSh28GST or Alum alone was administered to this group at day 150. In view of the results obtained, another group of healthy volunteers (n = 8) received two doses of 300 µg of rSh28GST, again with a 28-day interval. A six-month follow-up was performed with both clinical and biological evaluations. Immunogenicity of the vaccine candidate was evaluated in terms of specific antibody production, the capacity of sera to inhibit enzymatic activity of the antigen, and in vitro cytokine production. PRINCIPAL FINDINGS: Among the 24 healthy male participants no serious adverse events were reported in the days or weeks after administration. Four subjects under rSh28GST reported mild reactions at the injection site while a clinically insignificant increase in bilirubin was observed in 8/24 subjects. No hematological nor biochemical evidence of toxicity was detected. Immunological analysis showed that rSh28GST was immunogenic. The induced Th2-type response was characterized by antibodies capable of inhibiting the enzymatic activity of rSh28GST. CONCLUSIONS: rSh28GST in Alum did not induce any significant toxicity in healthy adults and generated a Th2-type immune response. Together with previous preclinical results, the data of safety, tolerability and quality of the specific immune response provide evidence that clinical trials with rSh28GST could be continued in humans as a potential vaccine candidate against urinary schistosomiasis.

Prediction of one-hour running performance using constant duration tests.

Critical velocity (CV) represents, theoretically, the highest velocity that can be sustained without fatigue. The aim of this study was to compare CV computed from 5 mathematical models in order to determine which CV estimate is better correlated with 1-hour performance and which model provides the most accurate prediction of performance. Twelve trained middle- and long-distance male runners (29 +/- 5 years) performed 3 randomly ordered constant duration tests (6, 9, and 12 minutes), a maximal running velocity test for the estimation of CV, and a 1-hour track test (actual performance). Two linear, 2 nonlinear, and 1 exponential mathematical models were used to estimate CV and to predict the highest velocity that could be sustained during 1 hour (predicted performance). Although all CV estimates were correlated with performance (0.80 < r < 0.93, p < 0.01), it appeared that CV estimated from the exponential model was more closely associated with performance than all other models (r = 0.93; p < 0.01). Analysis of the bias +/- 95% interval of confidence between actual and predicted performance revealed that none of the models provided an accurate prediction of the 1-hour performance velocity. In conclusion, the estimation of CV allows us to rank middle- and long-distance runners with regard to their ability to perform well in long-distance running. However, no models provide an accurate prediction of performance that could be used as a reference for coaches or athletes.