safety and immunogenicity of co-administered hookworm vaccine candidates na-gst-1 and na-apr-1 in gabonese adults

Conditions: Hookworm Infection; Hookworm Disease

Summary: na-gst-1 and na-apr-1 are proteins expressed during the adult stage of the necator americanus hookworm life cycle that are thought to play a role in the parasite's degradation of host hemoglobin for use as an energy source. vaccination with recombinant gst-1 or apr-1 has protected dogs and hamsters from infection in challenge studies. this study will evaluate the safety and immunogenicity of co-administering na-gst-1 and na-apr-1 to healthy gabonese adults living in an area of endemic hookworm infection.

double-blind, randomized, controlled dose-escalation phase 1 clinical trial in hookworm exposed adults. study site: centre de recherches médicales de lambaréné number of participants: 32 in 2 cohorts of 16 doses of na-gst-1 to be tested: 30 and 100 μg doses of na-apr-1 to be tested: 30 and 100 μg dose of gla-af: 5 μg per antigen cohort 1: 30 μg of each of the two antigens (na-gst-1/alhydrogel® and na-apr-1 (m74)/alhydrogel®) or hepatitis b vaccine; cohort 2: 100 μg of each of the two antigens (na-gst- 1/alhydrogel® and na-apr-1 (m74) /alhydrogel®) or hepatitis b vaccine. randomization: cohort 1: 30 μg na-gst-1 + 30 μg na-apr-1 (m74) (n = 12) versus hepatitis b vaccine/placebo (n = 4) cohort 2: 100 μg na-gst-1 + 100 μg na-apr-1 (m74) (n = 12) versus hepatitis b vaccine + placebo (n = 4) the cohorts will be enrolled in a staggered fashion with safety data assessed prior to the na-gst-1 and na-apr-1 dose escalation from 30 to 100 µg. pre-treatment: albendazole (400 mg) at least 2 weeks prior to first vaccination immunization schedule: study days 0, 28 and 180 route: intramuscular in the deltoid muscle study duration: approximately 20 months; each participant will be followed for a total of 12 months.

Eligibility criteria:
inclusion criteria: * males or females between 18 and 50 years, inclusive, who are long-term residents of gabon. * good general health as determined by means of the screening procedure. * assumed availability for the duration of the trial (12 months). * willingness to participate in the study as evidenced by signing the informed consent document. * negative for hookworm during screening, or if found to be infected with hookworm, has completed a course of three doses of albendazole. exclusion criteria: * pregnancy as determined by a positive urine hcg (if female). * participant unwilling to use reliable contraception up until one month following the third immunization (if female and not surgically sterile, abstinent or at least 2 years post-menopausal). * currently lactating and breast-feeding (if female). * inability to correctly answer all questions on the informed consent comprehension questionnaire. * evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, diabetes, or renal disease by history, physical examination, and/or laboratory studies. * known or suspected immunodeficiency. * laboratory evidence of liver disease (alanine aminotransferase \[alt\] greater than 1.25-times the upper reference limit). * laboratory evidence of renal disease (serum creatinine greater than 1.25-times the upper reference limit, or more than trace protein or blood on urine dipstick testing). * laboratory evidence of hematologic disease (absolute leukocyte count \ 11.0 x 103/mm3; hemoglobin \<10.000 g/dl \[females\] or \<12.0 g/dl \[males\]; or, platelet count \<140,000/mm3). * other condition that in the opinion of the investigator would jeopardize the safety or rights of a volunteer participating in the trial or would render the subject unable to comply with the protocol. * participation in another investigational vaccine or drug trial within 30 days of starting this study or for the duration of the study. * volunteer has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months. * history of a severe allergic reaction or anaphylaxis. * severe asthma as defined by the need for daily use of inhalers or emergency room/clinic visit or hospitalization within 6 months of the volunteer's planned first vaccination in the study. * positive for hcv * positive elisa for hbsag. * positive for hiv infection * use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this study or expect to use for the duration of the study. * receipt of a live vaccine within past 4 weeks or a killed vaccine within past 2 weeks prior to entry into the study. * history of a surgical splenectomy. * receipt of blood products within the 6 months prior to entry into the study. * previous receipt of a primary series of any hepatitis b vaccine.

Keywords: human hookworm necator americanus hookworm hookworm disease iron-deficiency anemia soil-transmitted helminth infection neglected tropical disease na-apr-1 na-gst-1