Safety and Immunogenicity of Co-Administered Hookworm Vaccine Candidates Na-GST-1 and Na-APR-1 in Gabonese Adults

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 \<3500/mm3; 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.