A Phase I Clinical Trial Immunizing Healthy Adults With the NMRC-M3V-Ad-PfCA Vaccine to Generate Biologic Reagents

This is an open label Phase 1 study of the Ad-PfCA vaccine designed to 1) provide reagents
for the development and refinement of cell-mediated immunoassays for measuring the human
immune response to candidate malaria vaccines (especially protective malaria vaccines such
as DNA/Ad-PfCA where better assays are needed to identify the correlates of protective
immunity) and 2) to provide a repository of antigen-specific PBMCs that can be used as
positive and negative controls in cell mediated immunoassays. The study group will consist
of up to 35 healthy adults aged 18 to 50 years who have been screened to meet inclusion and
exclusion criteria.

Subjects will be eligible for participation regardless of baseline adenovirus 5 serostatus.
At least 6 subjects will be "malaria naïve", meaning that 1) they have not been the
recipient of a malaria vaccine, 2) they have no history of malaria infection or travel to a
malaria endemic region within 6 months of first leukapheresis procedure or 60mL blood draw,
3) they have no history of long-term residence (>5 years) in an area known to have
significant transmission of P. falciparum, and 4) they have a negative P. falciparum
circumsporozoite (PfCSP) ELISpot assay at baseline. (From herein, for simplicity, we refer
to PfCSP simply as CSP). The remaining subjects will have no restrictions regarding receipt
of malaria vaccines, travel history or baseline CSP ELISpot results. Although it is more
difficult to recruit "malaria-naïve" subjects, the inclusion of at least 6 such subjects
should provide a more varied array of immune responses; this may be helpful for assay
development.

Eligible subjects will receive a single administration of the Ad-PfCA malaria candidate
vaccine at a dose of 2 x 1010 pu by intramuscular injection. Approximately 1 month
pre-immunization, study subjects will either have a large number of PBMCs collected by means
of leukapheresis, or a simple 60 mL blood draw, dependent upon initial pre-screening.
Pre-immunization samples designated for the repository do not require large volume sampling
of PBMCs. Rather, a 60 mL whole blood draw is sufficient for repository purposes. Thus,
subjects will be separated into sub-groups, dependent upon initial pre-screening. Subjects
whose samples are designated for the repository will undergo a simple, 60 mL blood draw in
lieu of leukapheresis #1 (sub-group A). Samples assigned for assay development will be
obtained from sub-group B.

Approximately 1 month post-immunization, study subjects in both sub-groups will have PBMCs
collected by means of leukapheresis. Consultation with immunology experts after
post-immunization screening will assist to identify those subjects whose samples do not meet
assay development or repository needs. In an effort to eliminate unnecessary procedures for
subjects, these individuals will not undergo a second leukapheresis, but will return for
their safety visit on day 84.

Prior to each leukapheresis/60 mL blood draw, a sample will be tested by CSP-ELISpot and
AMA1 ELISpot; the results will be used to categorize samples (see below). Follow up visits
will occur 2, 7, 14, 21, and 84 days following immunization. Depending on guidance from the
FDA, subjects will then be followed annually by phone, email, or mailings up to five years
from the time of immunization per FDA recommendation.

Inclusion Criteria:

- Healthy adults (male or non-pregnant, non-lactating female) 18 - 50 years of age
(inclusive)

- Available and willing to participate for duration of study

- Able and willing to provide written informed consent

- Able to complete an Assessment of Understanding with a score of at least 75% correct

- In good general health with no clinically significant health problems as established
by medical history, physical exam, and laboratory screening

- Men, and women of childbearing potential must agree to use effective means of birth
control from time of enrollment through the duration of the active phase of the study
(3 months following immunization)

- Women: Sexually active females, unless surgically sterile or at least one year
post-menopausal, must use an effective method of avoiding pregnancy (including oral
or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical
cap, abstinence, use of a condom by the sexual partner or sterile sexual partner)
prior to dosing of study vaccine, and must agree to continue using such precautions
for at least 3 months after immunization. Female subjects unable to bear children
must have a note from a Primary Care Provider as proof of her documentation (e.g.
tubal ligation or hysterectomy) or must be post-menopausal as appropriate by age with
at least one year of amenorrhea.

- Men must agree to use of effective means of birth control. If a male subject has had
a vasectomy this will be considered an adequate means of birth control.

- Agree to refrain from blood donation for one year after immunization

- Agree not to travel to a malaria endemic region during the active phase of the study

- Good peripheral venous access

Exclusion Criteria:

- Females who are pregnant (positive urine β-HCG) or nursing at screening or plan on
becoming pregnant or plan to nurse from time of screening through the duration of the
active phase of the study (3 months following immunization)

- Positive HIV, HBsAg or HCV serology

- An abnormal EKG, defined as one showing pathologic Q waves and significant ST-T wave
changes; left ventricular hypertrophy; any non-sinus rhythm excluding isolated
premature atrial contractions; right or left bundle branch block; or advanced
(secondary or tertiary) A-V heart block.

- Weight less than 110 pounds

- Use of systemic immunosuppressant pharmacotherapy (inhaled and topical steroids are
allowed) within 60 days of scheduled leukapheresis/60 mL blood draw or immunization

- Current significant medical condition (cardiovascular, pulmonary, hepatic, renal, or
hematological) or evidence of any other serious underlying medical condition
identified by medical history, physical examination, or laboratory examination
(includes bleeding disorders)

- Plan for surgery between screening visit and second (final) leukapheresis

- Known allergy to any component of the vaccine formulation

- Participation in any study involving another investigational vaccine or drug within
30 days prior to the first scheduled leukapheresis/60 mL blood draw or plan to
participate in another investigational vaccine/drug research study during
participation in the active phase of this study

- Receipt of immunoglobulin and/or any blood products within 90 days of scheduled
leukapheresis/60 mL blood draw or immunization

- Any other significant finding which, in the investigator's judgment, may
substantially increase the risk associated with the subject's participation in the
study or compromise the scientific objectives

- Risk factors for HIV exposure: unsafe sex and injectable drug use