Safety and Immune Response to a Clade C DNA HIV Vaccine
Safety and Immune Response to a Clade C DNA HIV Vaccine
The purpose of this study is to evaluate the safety and immune response to an HIV clade C DNA
 vaccine and to an MF59-adjuvanted clade C Env protein in healthy, HIV-uninfected adults.
This study will evaluate the safety, tolerability, and immunogenicity to DNA-HIV-PT123 (an
 HIV clade C DNA vaccine) and to Bivalent Subtype C gp120/MF59 in healthy, HIV-uninfected
 adults.

 The study will enroll healthy, HIV-uninfected participants aged 18 to 40 years. Participants
 will be randomly assigned to one of 6 groups. Each group will receive experimental vaccine
 and protein and/or placebo at 4 study visits. Participants in Groups 1-3 will receive all
 injections via needle and syringe. Participants in Groups 4-6 will receive the DNA vaccine
 via Biojector, and protein and/or placebo via needle and syringe.

 Participants in Groups 1 and 4 will receive the DNA vaccine at months 0, 1, 3, and 6 and the
 protein at months 3 and 6. Participants in Groups 2 and 5 will receive the DNA vaccine and
 the protein at months 0, 1, and 6 and placebo at month 3. Participants in Groups 3 and 6 will
 receive placebo at months 0, 1, 3, and 6.

 Study visits will include a physical examination, an interview and/or questionnaire, HIV
 testing and HIV risk-reduction counseling, and urine and blood collection. Participants may
 optionally choose to provide rectal fluid, cervical fluid, or semen samples.
Inclusion Criteria:

 General and Demographic Criteria

 -  Age of 18 to 40 years

 -  Access to a participating HVTN CRS and willingness to be followed for the planned
 duration of the study

 -  Ability and willingness to provide informed consent

 -  Assessment of understanding: volunteer demonstrates understanding of this study;
 provides answers to a questionnaire prior to first vaccination with verbal
 demonstration of understanding of all questionnaire items answered incorrectly

 -  Agrees not to enroll in another study of an investigational research agent

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

 HIV-Related Criteria:

 -  Willingness to receive HIV test results

 -  Willingness to discuss HIV infection risks and amenable to HIV risk reduction
 counseling.

 -  Assessed by the clinic staff as being at "low risk" for HIV infection and committed to
 maintaining behavior consistent with low risk of HIV exposure through the last
 required protocol clinic visit.

 Laboratory Inclusion Values:

 Hemogram/Complete blood count (CBC)

 -  Hemoglobin ≥ 11.0 g/dL for volunteers who were born female, ≥ 13.0 g/dL for volunteers
 who were born male

 -  White blood cell count = 3,300 to 12,000 cells/mm^3

 -  Total lymphocyte count ≥ 800 cells/mm^3

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

 -  Platelets = 125,000 to 550,000/mm^3 Chemistry

 -  Chemistry panel: ALT, AST, and ALP < 1.25 times the institutional upper limit of
 normal; creatinine ≤ institutional upper limit of normal.

 Virology

 -  Negative HIV-1 and -2 blood test: Sites may use locally available assays that have
 been approved by HVTN Laboratory Operations.

 -  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 Urine

 -  Normal urine:

 -  Negative urine glucose, and

 -  Negative or trace urine protein, and

 -  Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick, a
 microscopic urinalysis with red blood cells levels within institutional normal
 range).

 Reproductive Status

 -  Volunteers 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. Persons who are NOT of reproductive potential due to having
 undergone total hysterectomy or bilateral oophorectomy (verified by medical records),
 are not required to undergo pregnancy testing.

 Reproductive status: A volunteer who was born female must:

 -  Agree to consistently use effective contraception (Appendix B) for sexual activity
 that could lead to pregnancy from at least 21 days prior to enrollment through the
 last required protocol clinic visit.

 -  Effective contraception is defined as using 1 of the following methods:

 -  Condoms (male or female), or

 -  Diaphragm or cervical cap,

 -  PLUS 1 of the following methods:

 -  Intrauterine device (IUD),

 -  Hormonal contraception (in accordance with applicable national contraception
 guidelines),

 -  Successful vasectomy in the male partner (considered successful if a volunteer
 reports that a male partner has [1] documentation of azoospermia by microscopy,
 or [2] a vasectomy more than 2 years ago with no resultant pregnancy despite
 sexual activity after vasectomy); or

 -  Any other contraceptive method approved by the HVTN 111 PSRT

 -  Or not be of reproductive potential, such as having reached menopause (no menses for 1
 year) or having undergone hysterectomy, bilateral oophorectomy, or tubal ligation;

 -  Or be sexually abstinent. Volunteers 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 protocol clinic visit Other Volunteers 21
 years of age and older who were born female consenting to provide cervical samples:
 pap smear within the 3 years prior to enrollment, with the latest result reported as
 normal or ASCUS (atypical squamous cells of undetermined significance); for those 21
 years and older that have not had a pap smear within the last 3 years prior to
 enrollment, must be willing to undergo a pap smear with the result reported as normal
 or ASCUS prior to sample collection.

 Exclusion Criteria:

 General

 -  Blood products received within 120 days before first vaccination

 -  Investigational research agents received within 30 days before first vaccination

 -  Body mass index (BMI) ≥ 40; or BMI ≥ 35 with 2 or more of the following: systolic
 blood pressure > 140 mm Hg, diastolic blood pressure > 90 mm Hg, current smoker, known
 hyperlipidemia

 -  Intent to participate in another study of an investigational research agent during the
 planned duration of the HVTN 111 study

 -  Pregnant or breastfeeding Vaccines and other Injections

 -  HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received
 control/placebo in an HIV vaccine trial, the HVTN 111 PSRT will determine eligibility
 on a case-by-case basis.

 -  Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine
 trial. Exceptions may be made for vaccines that have subsequently undergone licensure
 by the FDA. For volunteers who have received control/placebo in an experimental
 vaccine trial, the HVTN 111 PSRT will determine eligibility on a case-by-case basis.
 For volunteers who have received an experimental vaccine(s) greater than 5 years ago,
 eligibility for enrollment will be determined by the HVTN 111 PSRT on a case-by-case
 basis.

 -  Live attenuated vaccines other than influenza vaccine received within 30 days before
 first vaccination or scheduled within 14 days after injection (eg, 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 (eg, 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 Immune System

 -  Immunosuppressive medications received within 168 days before first vaccination. (Not
 excluded from participation: [1] corticosteroid nasal spray; [2] inhaled
 corticosteroids; [3] topical corticosteroids for mild, uncomplicated dermatitis; or
 [4] a single course of oral/parenteral corticosteroids at doses < 2 mg/kg/day and
 length of therapy < 11 days with completion at least 30 days prior to enrollment.

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

 -  Immunoglobulin received within 60 days before first vaccination

 -  Autoimmune disease

 -  Immunodeficiency Clinically significant medical conditions

 -  Untreated or incompletely treated syphilis infection

 -  Clinically significant medical condition, physical examination findings, clinically
 significant abnormal laboratory results, or past medical history with clinically
 significant implications for current health. A clinically significant condition or
 process includes but is not limited to:

 -  A process that would affect the immune response,

 -  A process that would require medication that affects the immune response,

 -  Any contraindication to repeated injections or blood draws,

 -  A condition that requires active medical intervention or monitoring to avert
 grave danger to the volunteer's health or well-being during the study period,

 -  A condition or process for which signs or symptoms could be confused with
 reactions to vaccine, or

 -  Any condition specifically listed among the exclusion criteria below.

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

 -  Psychiatric condition that precludes compliance with the protocol. Specifically
 excluded are persons with psychoses within the past 3 years, ongoing risk for suicide,
 or history of suicide attempt or gesture within the past 3 years.

 -  Current anti-tuberculosis (TB) prophylaxis or therapy

 -  Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as
 defined in the most recent National Asthma Education and Prevention Program (NAEPP)
 Expert Panel report). Exclude a volunteer who:

 -  Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or

 -  Uses moderate/high dose inhaled corticosteroids, or

 -  In the past year has either of the following:

 -  Greater than 1 exacerbation of symptoms treated with oral/parenteral
 corticosteroids;

 -  Needed emergency care, urgent care, hospitalization, or intubation for
 asthma.

 -  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 last 12 months

 -  Hypertension:

 -  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 ≤ 140 mm Hg systolic
 and ≤ 90 mm Hg diastolic, with or without medication, with only isolated, brief
 instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg
 diastolic. For these volunteers, blood pressure must be ≤ 140 mm Hg systolic and
 ≤ 90 mm Hg diastolic at enrollment.

 -  If a person has NOT been found to have elevated blood pressure or hypertension
 during screening or previously, exclude for systolic blood pressure ≥ 150 mm Hg
 at enrollment or diastolic blood pressure ≥ 100 mm Hg at enrollment.

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

 -  Malignancy (Not excluded: Volunteer who has had malignancy excised surgically and who,
 in the investigator's estimation, has a reasonable assurance of sustained cure. or who
 is unlikely to experience recurrence of malignancy during the period of the study)

 -  Seizure disorder: History of seizure(s) within past three years. Also exclude if
 volunteer has used medications in order to prevent or treat seizure(s) at any time
 within the past 3 years.

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

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