Occurrence of unacceptable adverse events.

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.

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 <3000/mm3 or >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.