Initial Study of Malaria Vaccine Pfs25-EPA/Alhydrogel(Registered Trademark)

A vaccine to interrupt malaria transmission would be a valuable tool for local elimination
or eradication of this disease. Pfs25, a surface antigen of ookinetes in the mosquito stage
of P. falciparum, is a lead candidate for a malaria transmission blocking vaccine.
Recombinant Pfs25 has been conjugated to Pseudomonas aeruginosa ExoProtein A (EPA), and
adjuvanted with Alhydrogel(Registered Trademark). This open label, dose escalating Phase 1
study in malaria na ve adults, conducted at Johns Hopkins Bloomberg School of Public Health
Center for Immunization Research (CIR) in Baltimore, Maryland, will determine initial safety
and immunogenicity of the vaccine given on a 2-dose and 3-dose schedule. Thirty (30)
volunteers will be enrolled, with 5 receiving the low dose (8 micro g of conjugated Pfs25),
5 receiving the middle dose (16 micro g of conjugated Pfs25), and 20 receiving the high
dose (47 micro g of conjugated Pfs25). The high dose group will receive either 2 or 3 doses
of vaccine, on a 0, 2 month or 0, 2, 4 month vaccination schedule. Volunteers will be
followed for 12 months following the last vaccination. Safety outcomes will be local and
systemic adverse events (AEs). Immunogenicity outcomes will be antibody responses as
measured by ELISA, transmission blocking in a standard membrane feeding assay, and B and T
cell responses.

- INCLUSION CRITERIA:

All of the following criteria must be fulfilled for a volunteer to participate in this
trial:

- Age between 18 and 50 years.

- Good general health as a result of review of medical history and/or clinical testing
at the time of screening.

- Available for the duration of the trial.

- Willingness to participate in the study as evidenced by signing the informed consent
document.

- If female: subject is willing to use reliable contraception methods for the period of
at least 1month (2 months for oral contraceptive pills) prior to first vaccination to
3 months after last vaccination. Reliable methods of birth control include:
pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery;
condoms with spermicide; diaphragm with spermicide; surgical sterilization; vaginal
ring; transdermal patch; intrauterine device; abstinence; and post-menopause.

EXCLUSION CRITERIA:

A volunteer will be excluded from participating in this trial if any one of the following
criteria is fulfilled:

- Pregnancy as determined by a positive urine or serum human choriogonadotropin
(Beta-hCG) test at any point during the study (if female).

- Currently is lactating and breast-feeding (if female).

- Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator
affects the ability of the participant to understand and cooperate with the study
protocol.

- Neutropenia as defined by an absolute neutrophil count < 1500/mm(3).

- Alanine transaminase (ALT) level above the laboratory-defined upper limit of normal.

- Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic,
endocrine, rheumatologic, autoimmune, hematological, or renal disease by history,
physical examination, and/or laboratory studies including urinalysis.

- Other condition that in the opinion of the investigator would jeopardize the safety
or rights of a participant participating in the trial or would render the subject
unable to comply with the protocol.

- History of receiving any investigational product within the past 30 days.

- Receipt of antimalarial prophylaxis during the past 12 months, or planned travel to a
destination which would require malaria prophylaxis during the period of
participation.

- Prior malaria infection by history.

- Participant 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 2 years, or that requires the use of oral or
parenteral corticosteroids.

- Clinically significant reactive airway disease that does not respond to
bronchodilators.

- Positive ELISA and confirmatory Western blot tests for HIV-1.

- Positive ELISA and confirmatory tests for hepatitis C virus (HCV).

- Positive hepatitis B surface antigen (HBsAg) by ELISA.

- Pre-existing autoimmune or antibody-mediated diseases including but not limited to:
systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's
syndrome, or autoimmune thrombocytopenia.

- Known immunodeficiency syndrome.

- 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 starting this 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 past 6 months.

- Previous receipt of an investigational malaria vaccine.

- Refusal to allow storage of samples for future research.

- Any medical, psychiatric, social, or occupational condition or other responsibility
that, in the judgment of the Principal Investigator (PI), would interfere with the
evaluation of study objectives.