- Malaria is a severe infection caused by a parasite. People can get malaria if a mosquito
that carries the parasite bites them. Malaria infection does not happen in the United States,
but many people in Africa, Asia, and South America are at risk for it. Researchers want to
test two vaccines that may help decrease malaria infection.
- To see if two vaccines (Pfs25M-EPA/Alhydrogel and Pfs230DIM-EPA/Alhydrogel ) are safe in
humans and cause an immune response that will prevent malaria parasites from correctly
growing in the mosquito.
- Healthy adults ages 18 50.
- There are several groups in this study. Each group will receive a different dose of the
vaccine and some groups will received both vaccines.
- Vaccinations will be given on two days about 4 weeks apart.
- Participants will receive each vaccine as an injection into the arm. Blood will be drawn
on the day of vaccination.
- In the 4 weeks after receiving a vaccination, participants will have at least 3 clinic
visits and 1 phone contact. They will have at least 3 more visits and 3 phone contacts
over the next 6 months.
- At each visit, participants will be evaluated for side effects to the vaccine and any
new health changes or problems. They will be asked how they are feeling and if they have
taken any medicine. Blood and urine samples may be taken at the visit. More follow-up
visits may be needed to follow up on changes or problems.
A vaccine to interrupt malaria transmission would be a valuable tool for local elimination or
eradication of this disease. Pfs25 and Pfs230, surface antigens of zygotes and ookinetes in
the mosquito stage of Plasmodium falciparum, are the lead candidates for a malaria
transmission blocking vaccine. Recombinant Pfs25M and recombinant Pfs230D1M have each been
conjugated to Pseudomonas aeruginosa ExoProtein A (EPA) and adjuvanted with Alhydrogel . This
dose-escalating phase 1 study will determine safety and immunogenicity of these vaccines in
US adults and subsequently in Malian adults.
A total of 260 subjects will be enrolled at sites in the US and Mali to receive escalating
doses of Pfs25M- EPA/Alhydrogel , Pfs230D1M-EPA/Alhydrogel , or simultaneous
Pfs25MEPA/Alhydrogel and Pfs230D1M-EPA/Alhydrogel . Enrollment within each group will be
staggered for additional safety, and subjects will only be enrolled into the simultaneous
administration group once each individual dose has been administered and reviewed for safety.
Subjects will be followed for at least 6 months after the last vaccination. Safety outcomes
will be local and systemic adverse events (AEs) and serious adverse events (SAEs).
Immunogenicity outcomes will be antibody responses as measured by ELISA against recombinant
Pfs25, Pfs230, and EPA, and B cell responses. Functional activity of the induced antibodies
will be assessed by membrane feeding assays conducted at the National Institute of Allergy
and Infectious Diseases in the US.
- INCLUSION CRITERIA: (US & Mali)
All of the following criteria must be fulfilled for a volunteer to participate in this
1. Age greater than or equal to18 and less than or equal to 50 years.
2. Available for the duration of the trial.
3. Able to provide proof of identity to the satisfaction of the study clinician
completing the enrollment process.
4. In good general health and without clinically significant medical history.
5. Females of childbearing potential must be willing to use reliable contraception (as
defined below) from 21 days prior to Study Day 0 to 3 months after the last
- Reliable methods of birth control include one of the following: confirmed
pharmacologic contraceptives (parenteral) delivery; intrauterine or implantable
- Reliable methods of birth control include concurrent use of a pharmacologic and a
barrier method, i.e. two of the following: confirmed pharmacologic contraceptives
(oral, transdermal) delivery or vaginal ring AND condoms with spermicide or
diaphragm with spermicide.
- Abstinence of potentially reproductive sexual activity.
- Non-childbearing women will also be required to report date of last menstrual
period, history of surgical sterility (i.e. tubal ligation, hysterectomy) or
premature ovarian insufficiency (POI), and will have a baseline urine or serum
pregnancy test performed.
6. Willingness to have blood samples stored for future research.
7. Willingness to undergo direct skin feeds (Mali only).
8. Known resident of Bancoumana or surrounding area (Mali only).
EXCLUSION CRITERIA: (US & Mali)
A subject will be excluded from participating in this trial if any one of the following
1. Pregnancy as determined by a positive urine or serum human choriogonadotropin ( <=-
hCG) test (if female).
NOTE: Pregnancy is also a criteria for discontinuation of any further dosing or
nonsafety related interventions for that subject.
2. Currently breast-feeding (if female).
3. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator
affects the ability of the participant to understand and comply with the study
4. Hemoglobin, WBC, absolute neutrophils, and platelets outside the local
laboratorydefined limits of normal (subjects may be included at the investigator s
discretion for not clinically significant values outside of normal range).
5. Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined
upper limit of normal (subjects may be included at the investigator s discretion for
not clinically significant values outside of normal range).
6. Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or
hepatitis B (HBV).
7. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine,
rheumatologic, autoimmune, hematological, oncologic, or renal disease by history,
physical examination, and/or laboratory studies including urinalysis.
8. History of receiving any investigational product within the past 30 days.
9. Participation or planned participation in a clinical trial with an investigational
product prior to completion of the follow up visit 28 days following last vaccination
OR planned participation in an investigational vaccine study until the last required
10. Subject has had medical, occupational, or family problems as a result of alcohol or
illicit drug use during the past 12 months.
11. History of a severe allergic reaction or anaphylaxis.
12. Severe asthma, defined as asthma that is unstable or required emergent care, urgent
care, hospitalization, or intubation during the past 2 years, or that has required the
use of oral or parenteral corticosteroids at any time during the past 2 years.
13. Pre-existing autoimmune or antibody-mediated diseases including but not limited to:
systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis,
Sj(SqrRoot)(Delta)gren s syndrome, or autoimmune thrombocytopenia.
14. Known immunodeficiency syndrome.
15. Known asplenia or functional asplenia.
16. Use of chronic (greater than or equal to 14 days) oral or intravenous corticosteroids
(excluding topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day)
or immunosuppressive drugs within 30 days of Study Day 0.
17. Prior to Study Day 0 and every subsequent vaccination day, receipt of a live vaccine
within the past 4 weeks or a killed vaccine within the past 2 weeks.
18. Receipt of immunoglobulins and/or blood products within the past 6 months.
19. Previous receipt of an investigational malaria vaccine in the last 5 years.
20. Other condition that in the opinion of the investigator would jeopardize the safety or
rights of a participant participating in the trial, interfere with the evaluation of
the study objectives, or would render the subject unable to comply with the protocol.
21. Prior malaria infection by history in the last 10 years (US only).
22. Prior travel to a malaria transmission area in the last 5 years or planned travel
during the course of the study (US only).
23. History of severe reaction to mosquito bites (Mali only).
24. History of allergy to any component of the comparator vaccine (e.g. neomycin) (Mali
INCLUSION AND EXCLUSION FOR LARGE VOLUME BLOOD DRAW:
- Individuals previously enrolled in Arms A2, B2, or C2 may be asked to return to the
clinic for a single additional visit. This visit would be to collect a single large
volume blood sample for additional serological analysis and characterization of B cell
INCLUSION CRITERIA (LARGE VOLUME BLOOD DRAW):
-The following criteria must be fulfilled for a volunteer to participate in the large
volume blood draw addendum:
-- Previously enrolled in 15-I-0044 in Arms A2, B2, or C2
EXCLUSION CRITERIA (LARGE VOLUME BLOOD DRAW):
- A subject will be excluded from participating in the large volume blood draw
addendum if any one of the following criteria is fulfilled:
- Pregnancy as determined by self report (if female).
- Within the past 30 days has received a research drug or vaccine or been enrolled
in another research drug or vaccine trial.
- Condition or on a medication that in the opinion of the investigator would
jeopardize the safety or rights of a participant participating in the trial,
interfere with the evaluation of the study objectives, or would render the
subject unable to comply with the protocol.