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

Condition(s) targeted: HIV Infections

Intervention: SAAVI DNA-C2 vaccine (Biological); SAAVI MVA-C vaccine (Biological); Placebo (Biological)

Phase: Phase 1

Status: Recruiting

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Glenda Gray, Study Chair, Affiliation: University of the Witswatersrand
Kenneth Mayer, Study Chair, Affiliation: Fenway Community Health

The purpose of this study is to evaluate the safety of and immune response to an experimental DNA HIV vaccine followed by boosting with an experimental modified vaccinia HIV vaccine (MVA) in HIV uninfected adults.

Official title: A Phase 1 Placebo-Controlled Clinical Trial to Evaluate the Safety and Immunogenicity of SAAVI DNA-C2 Vaccine Boosted by SAAVI MVA-C Vaccine in HIV Uninfected Healthy Vaccinia Naive Adult Participants in South Africa and the United States

Study design: Prevention, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety Study

Primary outcome: Signs and symptoms of local and systemic reactogenicity, laboratory measures of safety, and adverse events

Secondary outcome:

T-cell responses as detected by HIV-1 specific interferon-gamma ELISspot and/or interferon-gamma/interleukin-2 intracellular cytokine staining

HIV-1-specific neutralizing and binding antibody assays

Detailed description: 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.

This study will last 12 months. 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. Risk-reduction counseling will be conducted at all study visits.

Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

18-45 years of age

Laboratory test results within specified ranges [complete blood count, chemistries, cardiac troponin 1, 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

Fenway Community Health Clinical Research Site, Boston, Massachusetts 02115, United States; Recruiting
Maarit E. Kelvin, RN, Phone: 401-793-4710, Email: mkelvin@fenwayhealth.org
Kenneth H. Mayer, MD, Principal Investigator

Brigham and Women's Hospital CRS, Boston, Massachusetts 02115, United States; Recruiting
Lizanne C. Noble, MPH, Phone: 617-732-5394, Email: lnoble@partners.org
Lindsey R. Baden, MD, Principal Investigator

Univ. of Rochester HVTN CRS, Rochester, New York 14642-0001, United States; Not yet recruiting
Catherine A. Bunce, RN, MS, CCRC, Phone: 585-275-5744, Email: catherine_bunce@urmc.rochester.edu
Michael C. Keefer, MD, Principal Investigator

Click here for more information about preventive HIV vaccines

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Related publications:

Hanke T, McMichael AJ, Dorrell L. Clinical experience with plasmid DNA- and modified vaccinia virus Ankara-vectored human immunodeficiency virus type 1 clade A vaccine focusing on T-cell induction. J Gen Virol. 2007 Jan;88(Pt 1):1-12. Review.

Verrier F, Burda S, Belshe R, Duliege AM, Excler JL, Klein M, Zolla-Pazner S. A human immunodeficiency virus prime-boost immunization regimen in humans induces antibodies that show interclade cross-reactivity and neutralize several X4-, R5-, and dualtropic clade B and C primary isolates. J Virol. 2000 Nov;74(21):10025-33.

Williamson C, Morris L, Maughan MF, Ping LH, Dryga SA, Thomas R, Reap EA, Cilliers T, van Harmelen J, Pascual A, Ramjee G, Gray G, Johnston R, Karim SA, Swanstrom R. Characterization and selection of HIV-1 subtype C isolates for use in vaccine development. AIDS Res Hum Retroviruses. 2003 Feb;19(2):133-44.

Last updated: June 24, 2009