This study will examine the safety and immune response of healthy adult volunteers to
AMA1-C1, an experimental malaria vaccine developed by the NIAID. Malaria affects about 300
million to 500 million people worldwide each year, causing from 2 million to 3 million
deaths. Increasing drug resistance to the malaria parasite, as well as widespread resistance
of mosquitoes (the insects that transmit the parasite) to pesticides are reducing the
ability to control malaria through these strategies. A vaccine that could reduce illness and
death from malaria would be a valuable new resource in the fight against this disease. Early
tests of AMA1-C1 in 66 people in the United States and in Mali, West Africa, found no
serious side effects of the vaccine. This study will test a shorter schedule of vaccinations
with AMA1-C1 than that used in the previous studies.
Healthy volunteers between 18 and 50 years of age who weigh at least 110 pounds and with no
travel to malaria endemic areas in the past 12 months may be eligible for this study.
Candidates are screened with a medical history and physical examination, blood and urine
tests, and a urine pregnancy test for women who are able to bear children.
Participants are randomly assigned to receive three injections of either the experimental
malaria vaccine or a placebo (a solution that does not contain the vaccine) over a 2-month
period. The shots are given in an upper arm muscle, each 1 month apart. On the day of each
injection, participants give a history of symptoms since the last visit, have a brief
physical examination and blood test and, for women, a blood or urine pregnancy test. After
the injection, participants remain in the clinic 60 minutes for observation. In addition to
the injections, participants undergo the following procedures:
- Record temperature and symptoms on a diary card daily for the first 7 days after each
- Follow-up clinic visits 1, 3, 7 and 14 days after each shot to check for side effects.
Blood samples are drawn before each injection and at each return clinic visit to check
the safety and immune response to the vaccine.
- Have apheresis, a special procedure that separates certain components of the blood, 7
days after each injection to measure the function of germ-fighting blood cells. For
this procedure, blood is drawn through a needle in an arm vein and directed into a
machine that separates the different types of blood cells. The white cells are
collected in a plastic ...
The study is a randomized, single-blinded (blinded to volunteers) placebo-controlled Phase 1
clinical trial in healthy adult volunteers designed to evaluate the safety and
reactogenicity of a new malaria blood stage vaccine candidate, and to elucidate the
immunogenicity of the antigen, AMA1-C1, formulated on Alhydrogel [R]. The trial will last 42
weeks. Volunteers will be recruited and screened, and those determined to be eligible will
be enrolled in the study, based on the inclusion and exclusion criteria described in Section
4.0 in this protocol. After providing written informed consent the volunteers will be
enrolled and randomly allocated to receive 80 microgram dose of AMA1-C1 formulated on
Alhydrogel [R] (12 volunteers) or Alhydrogel [R] alone (6 volunteers) at 0, 1 and 2 months.
After each injection, volunteers will be observed for 60 minutes for immediate reactions.
Volunteers will return to the clinic on study days 1, 3, 7, and 14 following each injection
for clinical assessment and collection of blood samples for evaluation of immune responses.
Leukaphereses will be performed 7 days after the third vaccination to obtain peripheral
blood mononuclear cells for B and T cell studies. Safety data for the cohort up to and
including follow up day 14 after the first, second and third injection will be available for
review by the Medical Monitor.
Immunogenicity of the vaccine will be assessed by standardized assays for antibody levels
against AMA1-3D7 and AMA1-FVO, and an in vitro growth inhibition assay (GIA). The cellular
basis of the immune responses will be evaluated by enumeration of relevant B and T cell
subpopulations, including total and antigen-specific naive, memory and effector
subpopulations specific for the antigens. The frequencies of B and T cells specific for the
vaccine antigens in the group that received AMA1-C1/ Alhydrogel [R] will be compared to
those in the group receiving Alhydrogel [R] alone. The total and antigen-specific cell
frequencies in pre-immune (day 0) samples will serve as additional negative controls for the
immunization. The goal of the study is to augment previously collected safety data for the
80 microgram antigen dose with a larger cohort, and to study the safety and immunogenicity
of an accelerated vaccination schedule.
- INCLUSION CRITERIA:
Males or females between 18 and 50 years, inclusive.
Available for the duration of the trial (34 weeks)
Willingness to participate in the study as evidenced by signing the informed consent
Weighing at least 110 pounds.
Age less than 18 years because insufficient data are available in adults to judge
potential risk in children.
Pregnancy as determined by a positive urine Beta-hCG (if female).
Participant unwilling to use reliable contraception methods (condoms or oral
contraceptives) for the duration of the trial (if female).
Currently lactating and breast-feeding (if female).
Participant unwilling to undergo apheresis.
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 (aspartate aminotransferase AST greater than the
upper limit of normal of the testing laboratory and/or total bilirubin levels greater than
the upper limits of normal of the testing laboratory).
Laboratory evidence of renal disease (serum creatinine greater than the upper limit of
normal of the testing laboratory).
Laboratory evidence of hematologic disease (absolute neutrophil count less than
1,500/mm(3); hemoglobin less than the lower limit of normal of the testing laboratory, by
sex; or platelet count less than 140,000/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 enrolling
in 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 to drugs or foods.
Asthma that has resulted in an emergency room visit or hospitalization within the last 6
Positive ELISA and confirmatory Western blot tests for HIV-1.
Positive ELISA and standard confirmatory tests for HCV.
Positive HBsAg by ELISA.
Known immunodeficiency syndrome.
Use of corticosteroids (excluding topical or nasal) or immunosuppressive drugs within 30
days of enrolling in this study or while the study is ongoing.
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 an investigational malaria vaccine.
Receipt of antimalarial prophylaxis during the past 12 months.
Prior malaria infection.
Travel to a malaria-endemic country during the past 12 months or planned travel to a
malaria-endemic country during the course of the study.
History of a known allergy to nickel.
History of known allergy to yeast.