Phase I Study of Safety and Immunogenicity of AMA1-C1Alhydrogel + CPG 7909 Vaccine for Malaria

AMA1-C1 + CPG 7909 is a blood stage malaria vaccine candidate. The primary objective of this Phase 1 study is to evaluate safety and reactogenicity of the vaccine in semi-immune adults in Mali. Secondary objectives are to evaluate the immunogenicity of the vaccine. The study is a double blind Phase 1 clinical trial in healthy adult volunteers. Volunteers will be screened and 24 participants will be enrolled and randomly assigned to one of the two groups: 12 volunteers will receive two doses of 80 microgram AMA1-C1/Alhydrogel + 500 microgram CPG; 12 volunteers will receive 80 microgram AMA1-C1/Alhydrogel, both at a 1-month dosing interval. Safety outcome measures are local and systemic (including laboratory) adverse events. Immune responses to vaccination will be measured by enzyme-linked immunosorbent assay (ELISA) and growth inhibition assay (GIA), and will be compared between groups. Peripheral blood lymphocytes will be assayed for the presence of AMA-1-specific memory B cells and for the total number of memory B cells.

• INCLUSION CRITERIA:

• Males or females between 18 and 45 years, inclusive.
• Known residents of the village of Don gu bougou, Mali.
• Good general health as determined by means of the screening procedure.
• Available for the duration of the trial (30 weeks).
• Willingness to participate in the study as evidenced by signing the informed consent document.

Exclusion criteria

• Pregnancy as determined by a positive urine beta-hCG at any point during the study (if female).
• If female, participant and her spouse have not used or are unwilling to use reliable contraceptive methods such as: abstinence, birth control pills or birth control patches or vaginal ring, diaphragm with spermicide, IUD (intrauterine device), condom with spermicide, progestin implant or injection, or surgical sterilization (hysterectomy, bilateral oophorectomy, tubal ligation) prior to enrollment to 3 months after the second vaccination. (At the time of vaccination a female participant must have a negative urine pregnancy test on two occasions at least two weeks apart, and must have used a reliable contraceptive method in the interim).
• Currently lactating and breast-feeding (if female).
• Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, chronic infectious or renal disease by history, physical examination, and/or laboratory studies including urinalysis.
• 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.
• Pre-existing known autoimmune diseases including but not limited to: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, autoimmune thrombocytopenia.
• Laboratory evidence of possible autoimmune disease determined by anti-dsDNA titer that equals or exceeds 25 IU.
• Laboratory evidence of liver disease (alanine aminotransferase [ALT] greater than 1.25 times the upper limit of normal of the testing laboratory).
• Laboratory evidence of renal disease (serum creatinine greater than the upper limit of normal of the testing laboratory, or more than trace protein or blood on urine dipstick testing confirmed by repeat testing of clean-catch, midstream sample). (More than trace blood on urine dipstick will not exclude a female who is actively menstruating.)
• Laboratory evidence of hematologic disease (absolute leukocyte count less than 3000/mm(3) or greater than 11,500/mm(3); hemoglobin less than 0.9 times the lower limit of normal of the testing laboratory, by gender; absolute granulocyte count less than 1300/ mm(3); absolute lymphocyte count less than 1000/mm(3); or platelet count less than 110,000/mm(3)).
• 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 while this study is ongoing.
• 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. This will be defined as:

• Asthma that is unstable or required emergent care, urgent care, hospitalization or intubation during the past two years or that requires the use of oral or parenteral corticosteroids;
• Clinically significant reactive airway disease that does not respond to bronchodilators.
• Positive rapid diagnostic test for anti-Hepatitis C virus (HCV).
• Positive rapid diagnostic test for Hepatitis B surface antigen (HBsAg).
• Known immunodeficiency syndrome.
• Use of systemic 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 non-live 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 an investigational malaria vaccine.
• History of a known allergy to nickel.
• History of known allergy to yeast.
• History of use of chloroquine or related compounds (amodiaquine or primaquine) within 8 weeks of study entry.