Safety of and Immune Response to Two HIV Vaccines: SAAVI DNA-C2 Boosted With SAAVIMVA-C, in HIV-Negative Adults

The worldwide HIV/AIDS epidemic may only be controlled through development and utilization
of a safe and effective vaccine that will prevent HIV infection. Due to the high prevalence
of HIV-1 subtype C in southern Africa, the South African AIDS Vaccine Initiative (SAAVI),
the HIV Vaccine Trials Network (HVTN) and the National Institute of Allergy and Infectious
Diseases (NIAID) are evaluating two subtype C HIV vaccines, SAAVI DNA-C2 and SAAVI MVA-C
through this study . These two vaccines will be used together in a prime-boost regimen. The
SAAVI DNA-C2 vaccine is a multigene DNA vaccine consisting of two DNA plasmids in equal
amounts that express an HIV-1 subtype C polyprotein comprising of Gag-Reverse
Transcriptase-Tat-Nef and an HIV-1 subtype C truncated Env. SAAVI MVA-C is a recombinant MVA
vaccine expressing the same immunogens as the SAAVI DNA-C2 vaccine. MVA is a highly
attenuated vaccinia virus. The purpose of this study is to evaluate the safety and
immunogenicity of an experimental DNA HIV vaccine, SAAVI DNA C2, followed by boosting with
an experimental recombinant MVA HIV vaccine, SAAVI MVA-C, in HIV uninfected adults.

Participants will actively participate in this study for 12 months and will then be
contacted and asked questions about their health once annually for 3 years following initial
study injection. Participants will be randomly assigned to receive either the SAAVI
prime-boost preventive vaccine regimen or placebo. Vaccination with the SAAVI DNA-C2 vaccine
will occur at Months 0, 1, and 2; boost vaccinations with the SAAVI MVA-C vaccine will occur
at Months 4 and 5. Additional study visits will occur at Weeks 2, 6, 10, 16, 18, and 20 and
Days 147, 154, 273, and 364.

Study procedures include physical exams, blood and urine collection, HIV testing, an
electrocardiogram, and questionnaire. Some blood collected from participants will be stored
and used in future research. Risk-reduction counseling will be conducted at all study
visits.

Inclusion Criteria:

- Laboratory test results within specified ranges [complete blood count, chemistries,
cardiac troponin T, urinalysis]

- Good general health

- HIV-1 and -2 uninfected

- Have access to a participating HIV Vaccine Trials Unit (HVTU) and willing to be
followed for the duration of the study

- Willing to receive HIV test results

- Negative hepatitis B surface antigen

- Negative hepatitis C virus (HCV) antibodies OR negative HCV PCR if anti-HCV test is
positive

- Willing to use acceptable forms of contraception from at least 21 days prior to
enrollment through the duration of the study

Exclusion Criteria:

- History of vaccination against smallpox

- HIV vaccines in prior HIV vaccine trial

- Immunosuppressive medications within 168 days prior to first study vaccination

- Blood products within 120 days prior to first study vaccination

- Immunoglobulin within 60 days prior to first study vaccination

- Live attenuated vaccines within 30 days prior to first study vaccination or scheduled
within 14 days after other vaccination (e.g., measles, mumps, and rubella [MMR]; oral
polio vaccine [OPV]; varicella; yellow fever; influenza vaccine in nasal form)

- Investigational research agents within 30 days prior to first study vaccination

- Any vaccines that are not live attenuated vaccines within 14 days prior to first
study vaccination

- Allergy treatment with antigen injections within 30 days prior to first vaccination
or scheduled within 14 days after vaccination

- Received investigational research agents within 30 days prior to first vaccination

- Current tuberculosis (TB) prophylaxis or therapy

- Recreational cocaine or methamphetamine use within the last 12 months prior to first
study vaccination

- Clinically significant medical condition, abnormal physical exam findings, abnormal
laboratory results, or past medical history that may affect current health. More
information about this criterion can be found in the protocol.

- Any medical, psychiatric, social, or job-related condition that would interfere with
the study

- Serious adverse reaction to vaccines. Participants who have had an adverse reaction
to pertussis vaccine as a child are not excluded.

- Hypersensitivity to eggs or egg products

- Electrocardiogram (ECG) with clinically significant findings. More information about
this criterion can be found in the protocol.

- Risk factors for heart disease. More information about this criterion can be found in
the protocol.

- History of or current heart disease. More information about this criterion can be
found in the protocol.

- Autoimmune disease or immunodeficiency

- Active syphilis infection. Participants with fully treated syphilis at least 6 months
prior to study entry are not excluded.

- Unstable asthma. More information about this criterion can be found in the protocol.

- Diabetes mellitus type 1 or 2. Participants with a history of isolated gestational
diabetes are not excluded.

- History of thyroid removal or of thyroid disease requiring treatment in the 12 months
prior to study entry

- Serious angioedema within the past 3 years or requiring medication within 2 years of
study entry

- Hypertension that is not well-controlled

- Body mass index (BMI) of 40 or more

- Bleeding disorder

- Cancer. Participants with surgically removed cancer that is unlikely to recur are not
excluded.

- Seizure disorder requiring medication within the last 3 years

- Absence of spleen

- Certain abnormal laboratory values

- Psychiatric condition that would interfere with compliance with the protocol

- Other conditions that, in the opinion of the investigator, would interfere with the
study

- Pregnancy or breastfeeding