Safety and Immune Response to Preventive HIV Immunization With Adenovirus Serotype 5 or 35 Vector

A Phase 1B Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant Adenoviral Subtype 35 (rAd35) and Subtype 5 (rAd5) HIV-1 Vaccines When Given as a Heterologous Prime-boost Regimen or as Boosts to a Recombinant DNA Vaccine in Healthy, Ad5-Naïve and Ad5-Exposed, Low Risk, HIV-1 Uninfected Adult Participants

This study will evaluate the safety and preliminary immune response to recombinant adenoviral serotype 35 and 5 HIV-1 vaccines in HIV-uninfected adults.

One of the more promising approaches in the development of a preventive HIV vaccine uses a DNA plasmid to prime the immune response to an adenoviral vector boost. This primary purpose of this study is to evaluate the safety, tolerability, and immune response to recombinant adenoviral serotype 35 (rAd35) and serotype 5 (rAD5) HIV-1 vaccines in Ad-5 naive and Ad-5 exposed HIV-uninfected adults.

This study will last approximately 12 months. Participants will include those who are both rAD5-naive and rAD5-exposed and will be stratified into one of four groups. Each group will consist of two arms, one interventional and one control. Participants in Groups 1, 2, and 3 will be rAD5-naive. Participants in Group 4 will be rAD5-exposed.

Participants in Group 1 will receive an injection of rAD35 vaccine or placebo at study entry and an injection of rAD5 vaccine or placebo at Month 6 with nine follow-up visits through Month 12. Participants in Groups 2, 3, and 4 will injections of DNA vaccinations or placebo at study entry and at Months 1 and 2, and an injection of rAD35 vaccine, rAD5 vaccine, or placebo at Month 6 with twelve follow-up visits though Month 12. A physical, questionnaire, and counseling will occur at all visits. Blood and urine collection will occur at most visits. A rectal swab will occur at selected visits. For females, a pregnancy test will occur at all visits.

Participants will be contacted for safety follow-ups after the injection every year for 5 years. Health and adverse events will be recorded. Participants will not need to return to the study clinic unless HIV confirmatory testing is needed.

Inclusion Criteria:

• Good general health
• Access to a participating HVTN clinical research site and willingness to be followed for the duration of the study
• Assessment of understanding, including understanding of Step Study results
• Willing to receive HIV test results
• Willing to discuss HIV infection risks, agree to HIV risk reduction counseling, and willing to continue 5 years of annual follow-up contact
• Willing to commit to maintaining behavior consistent with low risk of HIV exposure through the last required protocol visit
• Considered low risk for HIV infection after clinical staff assessment. More information on this criterion can be found in the protocol.
• Certain laboratory values. More information on this criterion can be found in the protocol.
• Negative Hepatitis B surface antigen
• Negative anti-Hepatitis C virus antibodies
• For females, agree to use effective contraception from at least 21 days prior to enrollment through the last protocol visit. More information on this criterion can be found in the protocol.

Exclusion Criteria:

• HIV-infected
• Active drug or alcohol abuse within 12 months prior to study entry
• History of newly acquired sexually transmitted infections. More information on this criterion can be found in the protocol.
• Experimental vaccines received within 5 years prior to study entry
• Immunosuppressive medications received within 168 days prior to first vaccination
• Blood products received within 120 days prior to first vaccination
• Immunoglobulin received within 60 days prior to first vaccination
• Live attenuated vaccines received within 30 days prior to first vaccination
• Investigational research agents received within 30 days prior to first vaccination
• Intent to participate in another study of an investigational research agent during planned duration of the study
• Any vaccines that not live attenuated vaccines and were received within 14 days prior to first vaccination
• Allergy treatment with antigen injections within 30 days prior to first vaccination or scheduled within 14 days after first vaccination
• Clinically significant medical condition, findings, results, or history with implications for current health. More information on this criterion can be found in the protocol.
• Serious adverse reactions to vaccines
• Autoimmune disease
• Immunodeficiency
• Active Syphilis infection within the past 6 months
• Asthma. More information on this criterion can be found in the protocol.
• Diabetes mellitus
• Thyroidectomy or thyroid disease requiring medication during the last 12 months
• Hypertension. More information on this criterion can be found in the protocol.
• Body mass index greater than 35 or 40. More information on this criterion can be found in the protocol.
• Bleeding disorder
• Malignancy
• Seizure disorder
• Asplenia
• Psychiatric condition that precludes compliance with the protocol
• Any other clinically significant condition or laboratory abnormality that, in the opinion of the investigator, would interfere with the study
• Pregnant or breastfeeding