Evaluating the Safety of and Immune Response to the VSV-Indiana HIV Vaccine in Healthy, HIV-Uninfected Adults

Many HIV vaccines that are in development use a virus vector to deliver the vaccine into the
body's cells in order to elicit an immune response. Vesicular stomatitis virus (VSV) is a
vector that has been studied in animals. As an HIV vaccine vector, it has been shown to
prevent disease progression in monkeys infected with simian/human immunodeficiency virus
(SHIV). This study will evaluate the safety and immune response to the VSV-Indiana (one type
of VSV vector) HIV gag vaccine in healthy, HIV-uninfected adults. In addition, study
researchers will determine the maximum dose of the vaccine that can be safely tolerated.

This study will enroll healthy, HIV-uninfected adults. Five groups of participants will be
enrolled, with each subsequent group receiving a slightly higher dose of the vaccine. Within
each group, participants will be randomly assigned to receive the study vaccine or a placebo
vaccine. Study researchers will examine safety data and how participants react to the study
vaccine before enrolling the next group of participants. At baseline and Week 8,
participants will receive two injections of the study vaccine or placebo vaccine—one in each
upper arm at each time point. At the baseline study visit, all participants will undergo a
physical examination; mouth examination; a medical and medication history review; and
saliva, blood, and urine collection. Female participants will also take a pregnancy test.
Participants will complete questionnaires to assess mental status and receive counseling on
HIV risk reduction and pregnancy prevention. After receiving the vaccine, participants will
remain in the clinic for at least 30 minutes for observation and monitoring of side effects.
For 7 days after the vaccination, participants will record any side effects in a symptom
log.

Participants will attend study visits 3 days and 1 and 2 weeks after the baseline study
visit, at Week 8 for the second vaccination, 3 days and 1 and 2 weeks after the Week 8
visit, and at Months 5 and 8. Follow-up study visits will include select baseline study
procedures. Participants will be contacted annually for 3 years for follow-up health
monitoring.

Inclusion Criteria:

- Access to a participating HVTN Clinical Research Site (CRS) and willing to be
followed for the planned duration of the study

- Able and willing to provide informed consent

- Demonstrate understanding of this study by completing a questionnaire prior to first
vaccination, with verbal demonstration of understanding of all questionnaire items
answered incorrectly

- Willing to receive HIV test results

- Willing to discuss HIV infection risks, amenable to HIV risk reduction counseling,
and committed to maintaining behavior consistent with low risk of HIV exposure
through the last required study visit

- Willing to be contacted annually after completion of scheduled clinic visits for a
total of 3 years following initial study injection

- Agrees not to enroll in another study of an investigational research agent prior to
completion of last required study clinic visit (excludes annual contacts for safety
surveillance)

- In good general health as shown by medical history, physical exam, and screening
laboratory tests

- Assessed by the clinic staff as being at "low risk" of HIV infection

- Hemoglobin greater than or equal to 11.0 g/dL for participants who were born female,
greater than or equal to 13.0 g/dL for participants who were born male

- White blood cell (WBC) count of 3,300 to 12,000 cells/mm^3

- Total lymphocyte count greater than or equal to 800 cells/mm^3

- Remaining differential either within institutional normal range or with site
physician approval

- Platelets between 125,000 and 550,000/mm^3

- Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST),
alkaline phosphatase, and creatinine values less than or equal to institutional upper
limits of normal

- Negative HIV-1 and -2 blood test: participants in the United States must have a
negative Food and Drug Administration (FDA)-approved immunoassay (IA)

- Negative Hepatitis B surface antigen (HBsAg)

- Negative anti-Hepatitis C virus antibodies (anti-HCV) or negative HCV polymerase
chain reaction (PCR) if the anti-HCV is positive

- Normal urine: negative urine glucose, negative or trace urine protein, and negative
or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a microscopic
urinalysis must be within institutional normal range)

- Participants who were born female: negative serum or urine beta human chorionic
gonadotropin (β-HCG) pregnancy test performed prior to vaccination on the day of
initial vaccination

- Participants who were born female must agree to consistently use effective
contraception from 21 days prior to study entry through the last required study
clinic visit for sexual activity that could lead to pregnancy, or not be of
reproductive potential, or be sexually abstinent. More information on this criterion
can be found in the protocol.

- Participants who were born female must also agree not to seek pregnancy through
alternative methods, such as artificial insemination or in vitro fertilization until
after the last required study clinic visit

Exclusion Criteria:

- Excessive daily alcohol use, frequent binge drinking, chronic marijuana abuse, or any
other use of illicit drugs within the 6 months prior to study entry

- History of newly acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes
simplex virus type 2 (HSV2), chlamydia, pelvic inflammatory disease (PID),
trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma
venereum, chancroid, or hepatitis B within the 12 months prior to study entry

- Untreated or incompletely treated syphilis infection

- HIV vaccine(s) received in a prior HIV vaccine trial. For potential participants who
have received control/placebo in an HIV vaccine trial, the HVTN 090 Protocol Safety
Review Team (PSRT) will determine eligibility on a case-by-case basis.

- Non-HIV experimental vaccine(s) received within the 5 years prior to study entry in a
prior vaccine trial. Exceptions may be made for vaccines that have subsequently
undergone licensure by the FDA. For potential participants who have received
control/placebo in an experimental vaccine trial, the HVTN 090 PSRT will determine
eligibility on a case-by-case basis. For potential participants who have received an
experimental vaccine(s) greater than 5 years prior to study entry, eligibility for
enrollment will be determined by the PSRT on a case-by-case basis.

- Immunosuppressive medications received within 168 days before first vaccination (Not
excluded: [1] corticosteroid nasal spray for allergic rhinitis; [2] topical
corticosteroids for mild, uncomplicated dermatitis; or [3] oral/parenteral
corticosteroids given for non-chronic conditions not expected to recur [length of
therapy 10 days or fewer with completion at least 30 days prior to study entry].)

- Blood products received within 120 days before first vaccination

- Immunoglobulin received within 12 months before first vaccination

- Live attenuated vaccines other than influenza vaccine received within 30 days before
first vaccination or scheduled within 14 days after injection (e.g., measles, mumps,
and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever)

- Influenza vaccine or any vaccines that are not live attenuated vaccines and were
received within 14 days prior to first vaccination (e.g., tetanus, pneumococcal,
hepatitis A or B)

- Allergy treatment with antigen injections within 30 days before first vaccination or
that are scheduled within 14 days after first vaccination

- Investigational research agents received within 30 days before first vaccination

- Intent to participate in another study of an investigational research agent during
the planned duration of the HVTN 090 study

- Current anti-tuberculosis (TB) prophylaxis or therapy

- Clinically significant medical condition, physical examination findings, clinically
significant abnormal laboratory results, or past medical history with clinically
significant implications for current health. More information on this criterion can
be found in the protocol.

- Any medical, psychiatric, occupational, or other condition that, in the judgment of
the investigator, would interfere with or serve as a contraindication to study
adherence, assessment of safety or reactogenicity, or a participant's ability to give
informed consent

- Serious adverse reactions to vaccines, including anaphylaxis and related symptoms
such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not
excluded: a participant who had a nonanaphylactic adverse reaction to pertussis
vaccine as a child.)

- Autoimmune disease

- Immunodeficiency

- Asthma other than mild, well-controlled asthma. More information on this criterion
can be found in the protocol.

- Diabetes mellitus type 1 or type 2, including cases controlled with diet alone. (Not
excluded: history of isolated gestational diabetes.)

- Thyroidectomy, or thyroid disease requiring medication during the 12 months prior to
study entry

- History of hereditary angioedema, acquired angioedema, or idiopathic angioedema

- Hypertension:

1. If a person has been found to have elevated blood pressure or hypertension
during screening or previously, exclude for blood pressure that is not well
controlled. Well-controlled blood pressure is defined as consistently less than
or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg diastolic,
with or without medication, with only isolated, brief instances of higher
readings, which must be less than or equal to 150 mm Hg systolic and less than
or equal to 100 mm Hg diastolic. For these participants, blood pressure must be
less than or equal to 140 mm Hg systolic and less than or equal to 90 mm Hg
diastolic at study entry.

2. If a person has NOT been found to have elevated blood pressure or hypertension
during screening or previously, exclude for systolic blood pressure greater than
or equal to 150 mm Hg at study entry or diastolic blood pressure greater than or
equal to 100 mm Hg at study entry.

- Body mass index (BMI) greater than or equal to 40 or BMI greater than or equal to 35
with two or more of the following criteria: age greater than 45, systolic blood
pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg,
current smoker, known hyperlipidemia

- Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or
platelet disorder requiring special precautions)

- Cancer (Not excluded: a participant with a surgical excision and subsequent
observation period that in the investigator's estimation has a reasonable assurance
of sustained cure or is unlikely to recur during the period of the study.)

- Seizure disorder (any history of seizure)

- Neurological or neuropsychiatric disorder that may interfere with the assessment of
safety such as: frequent recurring headaches (e.g., a pattern of more than one
headache per month affecting activities of daily living [ADLs]/work, frequent or
severe/complicated migraines, cluster headaches), a chronic pain syndrome, dizziness,
history of meningitis or encephalitis, cranial/spinal/peripheral neuropathy, limb
weakness or paralysis, movement disorder, narcolepsy, stroke with sequelae,
moderate/severe major depressive disorder, or moderate/severe bipolar disorder

- Asplenia: any condition resulting in the absence of a functional spleen

- Psychiatric condition that precludes compliance with the study. Specifically excluded
are people with psychoses within the 3 years prior to study entry, ongoing risk of
suicide, or history of suicide attempt or gesture within the 3 years prior to study
entry.

- Pregnant or breastfeeding

- Lives with or cares for any of the following: a person less than or equal to 2 years
of age or greater than 65 years of age, a person who is immunocompromised (at risk of
opportunistic infection), or a person with a chronic lung disease (such as cystic
fibrosis or requiring daily oral corticosteroids or home oxygen)