The purpose of this clinical study is to evaluate safety and immunogenicity in adult healthy volunteers of the vaccine candidate against schistosomiasis named Bilhvax.
The development of an efficient vaccine against human schistosomiasis represents a major challenge for the improvement of health in many developing countries. Schistosomiasis affects millions people in numerous countries and hampers economical development of tropical areas. Although progress has been made for the limitation of the disease severity by chemotherapy, continuous re-infection and risks of drug resistance point to the necessary development of alternative strategies. It is widely agreed that immunological prevention of chronic parasitic infections will be extremely difficult to achieve. Conversely in some major helminth infections like schistosomiasis, where parasite eggs laying in the tissues is the exclusive cause of pathology and the elimination of eggs in nature is the source of transmission, inhibition of parasite fecundity might represent for the future a novel way to prevent the deleterious effects of these chronic infections in man. The concept to target by vaccination the cause of the pathology rather than the parasite itself would provide a potent tool to control a major chronic infection. After years of basic studies on effector and regulatory mechanisms of immune response against schistosomiasis it has been identify a schistosome molecule named glutathione S-transferase 28 kDa (28GST) presenting a potential as vaccine candidate. This 28GST have been cloned and named Bilhvax. It has been shown that immunization with such schistosome GST would dramatically decrease female worm fecundity and egg viability in various hosts. It was demonstrated that these anti-fecundity effects are associated with the production of antibodies neutralizing the GST enzymatic activities obtained through a Th2-type immune response. This correlation between anti-fecundity effects and inhibition-mediated antibodies demonstrated in several animal models was re-enforced by epidemiological studies showing that such acquired antibodies produced during infection could be detected in adult individuals naturally resistant to the re-infection. The present phase 1 clinical trial is conducted in healthy Caucasian volunteers to evaluate as primary endpoint the safety of the recombinant Sh28GST (rSh28GST) in Alum (named Bilhvax), a vaccine candidate against human urinary schistosomiasis. The secondary endpoint is to evaluate immunogenicity of Bilhvax, to determine the profile of the immune response, and to estimate the neutralizing capacity of the antibodies against the rSh28GST enzymatic activity. The recombinant S. haematobium 28GST expressed in yeast is produced by Eurogentec SA in GMP conditions.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
24
subcutaneous route at Day 0, Day 28, and Day 150 for the third administration of 100µg for Arm 1
Centre d'Investigation Clinique - CHRU de Lille
Lille, France
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances
Time frame: D1 : administration, clinical observation, clinical analysis
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances
Time frame: D21 : clinical observation, clinical analysis
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances
Time frame: D28 : administration, clinical observation, clinical analysis
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Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances
Time frame: D29 : clinical observation, clinical analysis
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances
Time frame: D120 : clinical observation, clinical analysis
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances
Time frame: D150 : administration, clinical observation, clinical analysis
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances
Time frame: D165 : clinical observation, clinical analysis
Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Local signs and symptoms included pain or tenderness, swelling, induration and erythema at the site of injection. Complete physical examination including an examination of general appearance, body weight and rectal temperature, head, eyes, ears, nose and throat, neck, skin, cardiovascular and respiratory system, abdominal system, nervous system, lymphatic area, blood pressure, pulse and respiratory rates. General signs and symptoms including fever, headache, nausea, vomiting, myalgia, arthralgia, irritability/fussiness and drowsiness, loss of appetite and sleep disturbances
Time frame: D180 : clinical observation, clinical analysis
Immunogenicity
Immunogenicity was evaluated by dosage of specific antibody production, capacity of sera to inhibit enzymatic activity of the antigen, and immune profile estimation by in vitro cytokines production assay.
Time frame: Day of first administration and D21, D28, D29, D49, D120, D150, D165 and D180