phase 1 trial of na-asp-2 hookworm vaccine in previously infected brazilian adults

Conditions: Hookworm Infection

Summary: na-asp-2 is a protein expressed during the larval stage of the n. americanus hookworm life cycle. vaccination with recombinant asp-2 has protected dogs and hamsters from infection in challenge studies. in a clinical study in hookworm-uninfected adults in the usa, na-asp-2 hookworm vaccine was safe and immunogenic. this study will evaluate its safety and immunogenicity in individuals living in an area of endemic hookworm infection.

* double-blind, randomized, controlled phase 1 clinical trial. * study site: americaninhas, minas gerais, brazil. * number of participants: 48 in three groups of 16, randomized to receive either na-asp-2 hookworm vaccine (n=36) or butang® hepatitis b vaccine (n=12). * study duration: 48 weeks; each participant will be followed for a total of 42 weeks. * immunization schedule: study days 0, 56 and 112. * route: im in the deltoid muscle. * dose of na-asp-2: 10, 50 and 100 µg for the first, second and third dose cohort, respectively. * dose of alhydrogel®: 800 µg for each dose of na-asp-2.

Eligibility criteria:
inclusion criteria: * males or females between 18 and 45 years, inclusive. * known residents of the municipality of novo oriente de minas, minas gerais, brazil. * good general health as determined by means of the screening procedure. * completed a 3-dose albendazole treatment for documented hookworm infection during the previous 3 months. * available for the duration of the trial (42 weeks). * willingness to participate in the study as evidenced by signing the informed consent document. exclusion criteria: * pregnancy as determined by a positive urine β-hcg (if female). * participant unwilling to use reliable contraception methods up until one month following the third immunization (if female). * 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, or renal disease by history, physical examination, and/or laboratory studies. * behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the volunteer to understand and cooperate with the study protocol. * laboratory evidence of liver disease (alanine aminotransferase \[alt\] greater than 64 u/l \[females\] or greater than 58 u/l \[males\]). * laboratory evidence of renal disease (serum creatinine greater than 1.1 mg/dl \[females\] or greater than 1.3 mg/dl \[males\], or more than trace protein or blood on urine dipstick testing). * laboratory evidence of hematologic disease (absolute leukocyte count \ 12.5 x 103/mm3; hemoglobin \<10.3 g/dl \[females\] or \<11.0 g/dl \[males\]; absolute lymphocyte count \<900/mm3; or platelet count \<120,000/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. * 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 regular use of inhalers or emergency clinic visit or hospitalization within the last 6 months. * positive elisa for hcv. * positive elisa for hbsag. * known immunodeficiency syndrome. * use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30 days of starting this 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 past 6 months. * previous receipt of a primary series of any hepatitis b vaccine. * history of allergy to yeast.

Keywords: vaccine hookworm phase 1 na-asp-2