Safety of and Immune Response to an Adenoviral HIV-1 Vaccine in Healthy Adults

HIV infection continues to spread at pandemic levels throughout the world. Control of this
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 26 preventive HIV-1 vaccine.

This study will last 12 months. Participants will be randomly assigned to one of four arms
that will receive different doses of the vaccine or placebo administered via intermuscular
injection. Participants in Arms 1, 2, and 3 will all receive 3 injections. Each injection
will contain the same dose of vaccine. Arm 4 will receive 2 injections of a dose of vaccine
that will be determined by the safety data from Arms 1, 2, and 3. Participants will be
enrolled sequentially, from lowest to highest dose of vaccine, into Arms 1, 2, and 3. Arms
will begin enrollment only following review of safety data from the previous group. After
the Day 42 safety data from Arms 1, 2, and 3 have been reviewed, the dose for Arm 4 will be
determined, and enrollment into that arm will begin.

There will be 10 study visits in this study, occurring at baseline and after 0.5, 1, 1.5, 2,
6, 6.5, 7, and 12 months. Participants in Arms 1, 2, and 3 will receive injections on Days
0, 28, and 168. Participants in Arm 4 will receive injections on Days 0 and 168.
Participants will be asked to record their temperature and other side effects in a symptom
log for 7 days after each injection. Risk reduction/pregnancy prevention counseling will
occur at visits 1 through 9, and physical exams and assessments of illness or adverse events
will occur at all visits. At most visits, blood, urine, and oral swab collection will occur.
At some visits, HIV testing and pregnancy testing will occur.

Once a year for 5 years following study entry, participants will attend a study visit or
will be contacted by study staff by telephone or e-mail for follow-up safety and health
monitoring. Some participants will also undergo a blood collection at these visits.

Inclusion Criteria:

- Good general health with 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

- Appropriate hemoglobin, white blood cell, lymphocyte, and platelet count values as
defined in the study protocol

- Certain laboratory values as defined in the study protocol

- Adequate contraception from at least 21 days prior to study entry through visit 10

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 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 and/or well-controlled asthma

- Active syphilis infection. Those fully treated for syphilis over 6 months prior to
study entry are not excluded.

- Diabetes mellitus type 1 or 2

- Thyroidectomy or thyroid disease requiring medication within 12 months prior to study
entry

- Angioedema in the 3 years prior to study entry if the episodes are considered serious
or have required medication within the last 2 years

- 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 a functional spleen

- Psychiatric condition within the last 3 years. More information on this criterion can
be found in the study protocol.

- Individuals at high-risk of acquiring HIV infection

- Presence of pre-existing neutralizing antibodies for Adenovirus 26

- Pregnancy or breastfeeding