Early Immune Responses to Vaccination - A Substudy to HVTN 205

Some of the first HIV vaccines were designed to trigger neutralizing antibody responses as a
way to prevent HIV infection. Unfortunately, the first versions of these vaccines were not
able to achieve their desired response. An alternative strategy to the antibody approach is
the stimulation of HIV-specific CD8 T-lymphocyte (CTL) responses. CTL responses were
previously demonstrated to play an important role in the control of simian immunodeficiency
virus (SIV), the HIV equivalent studied in rhesus macaque monkeys. Additionally, other
studies suggest CTLs play an important role in viral control during chronic infection. Based
on this information, several groups have shifted their focus to the development of CTL-based
vaccines, some of which have entered advanced clinical trials.

A DNA/rMVA vaccine strategy is structured to bring about both T cell and antibody responses.
The primary vaccination is DNA based and will express only HIV proteins as a way to produce
an HIV-focused immune response. A secondary, rMVA boost vaccination, which expresses both
HIV and MVA proteins will ideally amplify the focused response of the initial vaccination.
The DNA and rMVA are physically two different vaccinations given at separate times but
together they make up one preventive regimen. Both vaccine components express non-infectious
virus-like particles.

The main study, HVTN 205 will evaluate the safety of and immune response to a two vaccine
regimen in healthy, HIV-uninfected adults who never received an HIV preventive vaccine
before. HVTN 205 will include two parts, Part A, in which the two vaccine regimen is
compared to a placebo, and Part B, in which the two vaccine regimen will be compared to both
a placebo and a single vaccine regimen with the rMVA vaccine.

HVTN 908 is a sub study of HVTN 205, and will explore the innate immune response to
candidate HIV vaccines. In particular, researchers will study whether early immune response
following vaccination can predict strong and long-lasting immunity. They will also study
whether varying types of vaccines promote different immune responses soon after vaccination.

Only participants enrolled in HVTN 205 are eligible for HVTN 908. Approximately 50
participants will be recruited for the duration of 12 months per participant. The study will
last for a total of 2 years, including enrollment, follow-up, and analysis. Potential
participants of the sub study will undergo a screening visit before eligibility can be
determined. Screening may involve a physical exam, health history, and blood tests.

There will be some additional visits for participants of HVTN 908 that are not included in
the main study. Some main study visits may also take extra time for participants enrolled in
the sub study. Blood samples will be taken at study visits. These samples are taken in
addition to those for the main study.