Malaria Vaccine in Children in Mali

Apical membrane antigen-1 (AMA1) is a surface protein expressed during the asexual blood stage of P. falciparum. It is produced as an 83-kDa polypeptide by mature schizonts in infected erythrocytes. In clinical studies in malaria-unexposed adults in the USA and in malaria-exposed adults in Mali, AMA1-C1/Alhydrogel was safe and immunogenic. This study will evaluate its safety and immunogenicity in malaria-exposed children living in an area of seasonal malaria transmission.

• INCLUSION CRITERIA:

Males or females aged 2 to less than 4 years old. Children must be born no earlier than September 1, 2002 and must have had their second birthday prior to first vaccination.

Known residents of the village of Doneguebougou, Mali or Bancoumana.

Good general health as determined by means of the screening procedures.

Available for the duration of the trial (52 weeks).

Willingness to participate in the study as evidenced by parents/legal guardians signing or fingerprinting the informed consent document.

Exclusion criteria

Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, 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 or the parent/legal guardian to understand and cooperate with the study protocol.

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).

Laboratory evidence of hematologic disease (absolute leukocyte count less than 3000/mm(3) or greater than 14,500/mm(3), absolute lymphocyte count less than 1000/mm(3), platelet count less 120,000/mm(3), or hemoglobin less than 8.5 g/dL).

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.

History of a severe allergic reaction or anaphylaxis.

Severe asthma (emergency room visit or hospitalization within the last 6 months).

Positive ELISA for HCV.

Positive HBsAg by ELISA.

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 (e.g. measles/mumps/rubella (MMR)) or a non-live vaccine (e.g. diphtheria/pertussis/tetanus (DPT)) within past 2 weeks prior to entry into the study.

History of a surgical splenectomy.

Receipt of a blood transfusion 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.

Known hypersensitivity to any component of the Hib vaccine (tetanus toxoid, lactose).

Previous administration of Hib vaccines.

Known thrombocytopenia or bleeding disorders.