Safety and Immune Response to a Recombinant Adenovirus HIV-1 Vaccine in Healthy Adults

Control of the HIV pandemic can only be achieved with the development of a safe and effective
preventive HIV vaccine. A vaccine that will prevent HIV infection will elicit a strong immune
response from both CD4 and CD8 cells. Recombinant adenovirus serotype vectors have been shown
to elicit just such a response. The purpose of this study is to determine the safety and
immunogenicity of the recombinant adenovirus serotype 5 preventive HIV-1 vaccine.

This study will last 18 to 24 months. Participants will be randomly assigned to one of four
arms that will receive vaccine or placebo administered via intramuscular injection.
Participants in Arms 1, 2, and 3 will all receive 3 injections. Participants in Arm 4 will
receive one injection. For most participants, there will be 10 study visits in this study;
for participants in Arm 4, there will be only 7 visits. For Arms 1, 2, and 3, study visits
will occur at baseline and on Days 0, 14, 28, 42, 56, 168, 182,196, and 365. Participants in
Arms 1, 2, and 3 will receive injections on Days 0, 28, and 168. For participants in Arm 4,
study visits will occur at baseline and on Days 0, 14, 28, 56, 168 and 365. Participants in
Arm 4 will receive one injection only, on Day 0. Participants will be asked to record their
temperature and other side effects in a symptom log for 3 days after each injection. Risk
reduction/pregnancy prevention counseling and physical exams will occur at all visits. At
most visits, blood, urine, and oral swab collection will occur. Samples collected will be
stored for future testing. HIV testing and pregnancy testing will occur at select visits. At
Years 2, 3, 4, and 5, participants will be followed-up by telephone, e-mail, or study visit
to collect vital status, and information about any development of significant disability or
incapacity, hospitalizations, or congenital anomalies. At these follow-up visits, blood
collection will be optional.

Inclusion Criteria:

- Good general health

- Normal hematological, hepatic and renal functions

- Demonstrated understanding of study

- Willing to receive HIV test results

- HIV-1 and -2 uninfected

- Hepatitis B surface antigen negative

- Anti-hepatitis C virus (anti-HCV) negative antibody or negative HCV PCR if anti-HCV is
positive

- Adequate contraception. For more information on this criterion can be found in the
protocol.

Exclusion Criteria:

- HIV vaccines or placebos in prior HIV vaccine trial

- Immunosuppressive medications within 168 days prior to first injection. Participants
taking corticosteroid nasal spray or topical corticosteroids are not excluded.

- Blood products within 120 days prior to first injection

- Immunoglobulin within 60 days prior to first injection

- Investigational agents within 30 days prior to first injections

- Live attenuated vaccine within 30 days prior to first injection

- Any vaccine that is not a live attenuated vaccine within 14 days prior to first
injection

- Any clinically significant medical condition that, in the opinion of the investigator,
may interfere with the study

- Any medical, psychiatric, occupational, or social condition or responsibility that, in
the opinion of the investigator, would interfere with the study

- Serious adverse reaction to vaccines. Participants who had a nonanaphylactic adverse
reaction to pertussis vaccine as a child are not excluded.

- Known autoimmune disease

- Known immunodeficiency

- Asthma other than mild, well-controlled asthma

- Diabetes mellitus type 1 or 2

- Thyroidectomy or thyroid disease in the12 months prior to study entry

- Angioedema in the 3 years prior to study entry

- Hypertension. More information on this criterion can be found in the protocol.

- Body mass index (BMI) of 40 or higher OR BMI of 35 or greater, if other cardiovascular
risk factors. More information on this criterion can be found in the protocol.

- Bleeding disorder

- Malignancy, unless it has been surgically removed and, in the opinion of the
investigator, is not likely to recur during the study period

- Seizure disorder or occurrence of seizure in the 3 years prior to study entry.
Participants who have not required medications or had a seizure for prior 3 years are
not excluded.

- Absence of spleen

- Individuals at high-risk of acquiring HIV infection

- Presence of pre-existing neutralizing antibodies for Adenovirus 5 or 48

- Pregnancy or breastfeeding