Evaluating the Safety and Immune Response to an HIV Vaccine Boost Following the Administration of Two HIV Vaccines, in HIV-Uninfected, Healthy Adults (Study Extension to HVTN 073/SAAVI 102)

The HVTN 073/SAAVI 102 study is evaluating the safety of two experimental HIV vaccines—SAAVI
DNA-C2 and SAAVI MVA-C—given sequentially as a prime-boost regimen in healthy,
HIV-uninfected adults. This is an extension of that study and will enroll people who
participated in the HVTN 073/SAAVI 102 study. Previous studies have shown that a protein
vaccine boost to an HIV vaccine may improve antibody responses. This study will evaluate the
safety and immune response to an HIV envelope protein vaccine—the Sub C gp140 vaccine with
MF59 adjuvant—in healthy, HIV-uninfected adults who have previously participated in the HVTN
073/SAAVI 102 study. Study researchers will explore whether the addition of a protein boost
vaccine to the SAAVI DNA-C2 and SAAVI MVA-C vaccine regimen improves antibody response.

This study will enroll people who participated in the HVTN 073/SAAVI 102 study,regardless of
whether they received vaccine or placebo. Participants will be randomly assigned to receive
either the Sub C gp140 vaccine with MF59 adjuvant or a placebo injection during study visits
at baseline and Month 3. At the baseline and Month 3 visits, participants will undergo a
physical examination, HIV testing and counseling, pregnancy testing for female participants,
interviews and questionnaires, risk reduction counseling, and blood collection (at the
baseline visit only). They will then receive their assigned vaccine or placebo as one
injection in their upper arm. Participants will remain in the clinic for 30 minutes after
receiving the vaccination for observation and monitoring. For 3 days after the vaccination,
participants will record any side effects in a symptom log and make contact daily with the
study site staff.

Additional study visits will occur at Weeks 1 and 2, 1 and 2 weeks after the Month 3 visit,
and Months 6 and 9. At these visits, select baseline study procedures will occur. At Month
15, study staff will contact participants for follow-up health monitoring. Participants will
then complete any annual health contacts for the original HVTN 073/SAAVI 102 study.

Inclusion Criteria:

- Hemoglobin greater than or equal to 11.0 g/dL

- White blood cell (WBC) count greater than 2,500 cells/mm^3

- Platelets greater than or equal to 125,000/mm^3

- Chemistry panel: alanine aminotransferase (ALT), aspartate aminotransferase (AST),
and alkaline phosphatase less than 1.25 times the institutional upper limit of
normal; creatinine less than or equal to the institutional upper limit of normal

- Normal urine:

1. Negative urine glucose, and

2. Negative or trace urine protein, and

3. Negative or trace urine hemoglobin (if trace hemoglobin is present on dipstick,
a microscopic urinalysis within institutional normal range)

- Able and willing to provide informed consent

- Negative HIV-1 and -2 blood test: Participants must have a negative HIV test result
as specified by the HVTN Laboratory Program's in-study HIV diagnostic algorithm

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

- Reproductive status: A participant who was born female must agree to consistently use
effective contraception from at least 21 days prior to enrollment through 90 days
after the participant's final vaccination, for sexual activity that could lead to
pregnancy. 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 scheduled protocol visit

- Receipt of scheduled injection at visit 11 in the HVTN 073/SAAVI 102 study

Exclusion Criteria:

- Participant meets criteria for delay or discontinuation of vaccination or termination
from the study. More information on this criterion can be found in the protocol.

- Participant has an unresolved AE that is possibly, probably, or definitely related to
the study product

- Any medical, psychiatric, or social condition, or occupational or other
responsibility 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 participant's ability to give informed consent (e.g., a skin
condition overlying a potential injection site, which could interfere with
reactogenicity assessment)