HIV Vaccine in HIV-uninfected Adults
HIV Vaccine in HIV-uninfected Adults
The purpose of this study is to test whether delayed boosting (an extra administration of a
 vaccine) with the IHV01 (FLSC) protein and A244/AHFG with or without ALFQ will cause your
 body to make higher amounts of antibodies or different types of antibodies after the
 vaccination.
The purpose of this study is to define the safety and immunogenicity of IHV01 and A244/AHFG
 with and without ALFQ at a full dose and at a fractional dose (one-fifth of a full dose) in a
 late boost setting for participants who had previously received a late boost of AIDSVAX®B/E
 with or without ALVAC in RV306. Safety will be assessed through the frequency of the overall
 and specific post-vaccination reactions. Blood, lymph nodes, sigmoid tissue, and mucosal
 specimens/secretions will be collected to assess humoral, cell-mediated, innate, and mucosal
 immune responses.

 Healthy, HIV-uninfected participants, at a low risk for HIV infection, available for 12
 months, who were randomized to receive active vaccine in RV306 and completed all vaccinations
 will be enrolled. A total of 120 participants will be enrolled across four vaccination
 groups. In each group, 25 participants will receive IHV01 and A244/AHFG at a full or
 fractional dose with or without ALFQ and 5 participants will receive placebo. All injections,
 whether vaccine or placebo, will be a one-time intramuscular (IM) administration into the
 quadriceps muscle at study Day 0. Participants will be followed-up for up to 48 weeks after
 enrollment on days 1, 7, 14, 168 and 336. Mucosal secretion collections and endocervical
 cytobrush/swab procedures will be performed at Weeks 0, 2, 24, and 48 on consenting
 participants. Leukapheresis, sigmoid biopsy, and lymph node biopsy procedures will be
 performed only at Week 2 on consenting participants.
Inclusion Criteria:

 -  Healthy, HIV-uninfected male and female participants

 -  Prior RV306 recipients who were randomized to receive active vaccine with late
 boosting at month 12, 15, or 18 and who completed all vaccinations

 -  Have a Thai identity card

 -  Must be at low risk for HIV infection per investigator assessment

 -  Must be able to understand and complete the informed consent process

 -  Must be capable of reading Thai

 -  Must successfully complete a Test of Understanding prior to enrollment

 -  Must be in good general health without clinically significant medical history

 -  HIV-uninfected per diagnostic algorithm within 45 days of enrollment

 -  Laboratory screening analysis:

 1. Hemoglobin: Women ≥11.0 g/dL, Men ≥11.5 g/dL

 2. White cell count: 4,000 to 11,000 cells/mm3

 3. Platelets: 150,000 to 450,000/mm3

 4. ALT and AST ≤1.25 institutional upper limit of reference range

 5. Creatinine: ≤1.25 institutional upper limit of reference range

 6. Urinalysis (dipstick) for blood and protein no greater than 1+ and negative
 glucose

 -  Female-Specific Criteria:

 1. Not currently breastfeeding and not planning to become pregnant during the first
 3 months after study vaccine/placebo injection

 2. Negative pregnancy test for women at screening, prior to vaccination (same day),
 and prior to any of the invasive procedures

 3. Be using an adequate birth control method for 45 days prior to receipt of
 vaccine/placebo and for at least 3 months after receipt of the vaccine/placebo.
 Adequate birth control is defined as follows: Contraceptive medications delivered
 orally, intramuscularly, vaginally, or implanted, underneath the skin, surgical
 methods (hysterectomy or bilateral tubal ligation), condoms, diaphragms,
 intrauterine device, or abstinence

 -  Male-Specific Criteria:

 1. Be using an adequate birth control method for at least 3 months after receipt of
 the vaccine/placebo. For non-vasectomized male participants with female partners
 of child-bearing potential this includes the use of condoms or abstinence and/or
 their partner's use of contraceptive medications delivered orally,
 intramuscularly, vaginally, or implanted, underneath the skin, surgical methods
 (hysterectomy or bilateral tubal ligation), diaphragms, or intrauterine device.

 Exclusion Criteria:

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

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

 -  Women breast-feeding or pregnant (positive pregnancy test) or planning to become
 pregnant during the window between study enrollment and 3 months after the vaccination
 visit

 -  History of anaphylaxis or other serious adverse reaction to vaccines

 -  Volunteer has received any of the following substances:

 1. Chronic use of therapies that may modify immune response, such as IV immune
 globulin and systemic corticosteroids (in doses of > 20 mg/day prednisone
 equivalent for periods exceeding 10 days) Note: The following exceptions are
 permitted and will not exclude study participation: use of corticosteroid nasal
 spray for rhinitis, topical corticosteroids for an acute uncomplicated
 dermatitis; or a short course (duration of 10 days or less, or a single
 injection) of corticosteroid for a non-chronic condition (based on investigator
 clinical judgment) at least 2 weeks prior to enrollment in this study

 2. Blood products within 120 days prior to HIV screening

 3. Immunoglobulins within 30 days prior to HIV screening

 4. Any licensed vaccine within 14 days prior to initial study vaccine administration
 in the present study

 5. Receipt of any investigational HIV vaccine other than RV306 products

 6. Investigational research agents or vaccine within 30 days prior to enrollment in
 the present study

 7. Anti-tuberculosis prophylaxis or therapy during the past 90 days prior to
 enrollment

 -  Active sexually transmitted infection confirmed by clinical exam and diagnostic test

 -  Any medical, psychiatric, social condition, occupational reason, or other
 responsibility that, in the judgment of the investigator, is a contradiction to
 protocol compliance or impairs a volunteer's ability to give informed consent

 -  Psychiatric condition that precludes compliance with the protocol; past or present
 psychoses; past or present bipolar disorder; disorder requiring lithium; or within 5
 years prior to enrollment, a history of suicide ideation or attempt

 -  Study site employees who are involved in the protocol and/or may have direct access to
 study related area

 Final evaluation of eligibility will be based on the medical judgment of the investigator
 based on his/her medical and research experience.