Evaluating the Safety and Immune Response to Three Different DNA HIV Vaccines Administered With a MVA-CMDR Boost Vaccine in Healthy, HIV-Uninfected Adults

NCT02296541 | Completed Phase 1 DMC

• 2 other identifiers: HVTN 10611999
• Study Type: interventional
• Target: 105
• Locations: 2 countries
• Sites: 7

Brief Summary

The purpose of this study is to evaluate the safety and immune response to three DNA vaccines and a MVA-CMDR vaccine that may boost the immune response to the DNA vaccines in healthy, HIV-uninfected adults.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (13)

• Frequency of local and systemic injection site reactogenicity signs and symptoms for each type of vaccine

  Measured through Month 8

• Severity of local and systemic injection site reactogenicity signs and symptoms for each type of vaccine

  Measured through Month 8

• Frequency of adverse events (AEs)

  Categorized by MedDRA body system, MedDRA preferred term, severity, and assessed relationship to study products; detailed description of all AEs meeting Division of AIDS (DAIDS) criteria for expedited reporting (EAE)

  Measured through participant follow-up (3 and 5 years for participants in the United States and Switzerland, respectively)

• Laboratory measure of safety: measurement of white blood cells (WBC)

  Measured through Month 8

• Laboratory measure of safety: measurement of neutrophils

  Measured through Month 8

• Laboratory measure of safety: measurement of lymphocytes

  Measured through Month 8

• Laboratory measure of safety: measurement of hemoglobin

  Measured through Month 8

• Laboratory measure of safety: measurement of platelets

  Measured through Month 8

• Laboratory measure of safety: measurement of alanine aminotransferase (ALT)

  Measured through Month 8

• Laboratory measure of safety: measurement of aspartate aminotransferase (AST)

  Measured through Month 8

• Laboratory measure of safety: measurement of alkaline phosphatase

  Measured through Month 8

• Laboratory measure of safety: measurement of creatinine

  Measured through Month 8

• Number of participants with early discontinuation of vaccinations and reason for discontinuation

  Measured through Month 8

Secondary Outcomes (18)

• Response rate of CD4 T-cell responses 2 weeks after the last DNA vaccination

  Measured through Month 2.5

• Total magnitude of CD4 T-cell responses 2 weeks after the last DNA vaccination

  Measured through Month 2.5

• Response rate of CD8 T-cell responses 2 weeks after the last DNA vaccination

  Measured through Month 2.5

• Total magnitude of CD8 T-cell responses 2 weeks after the last DNA vaccination

  Measured through Month 2.5

• Breadth of CD4 T-cell responses determined by epitope mapping, 2 weeks after the last DNA vaccination

  Measured through Month 2.5

Study Arms (6)

Group 1: DNA Nat-B env and MVA-CMDR

EXPERIMENTAL

Participants will receive a single injection of DNA Nat-B env at Months 0, 1, and 2. They will receive a single injection of MVA-CMDR at Months 4 and 8.

Biological: DNA Nat-B env; Biological: MVA-CMDR

Group 1: Placebo vaccines for DNA Nat-B env and MVA-CMDR

PLACEBO COMPARATOR

Participants will receive a single injection of placebo for DNA Nat-B env at Months 0, 1, and 2. They will receive a single injection of placebo for MVA-CMDR at Months 4 and 8.

Biological: Placebo for DNA Nat-B env; Biological: Placebo for MVA-CMDR

Group 2: DNA CON-S env and MVA-CMDR

EXPERIMENTAL

Participants will receive a single injection of DNA CON-S env at Months 0, 1, and 2. They will receive a single injection of MVA-CMDR at Months 4 and 8.

Biological: DNA CON-S env; Biological: MVA-CMDR

Group 2: Placebo vaccines for DNA CON-S env and MVA-CMDR

PLACEBO COMPARATOR

Participants will receive a single injection of placebo for DNA CON-S env at Months 0, 1, and 2. They will receive a single injection of placebo for MVA-CMDR at Months 4 and 8.

Biological: Placebo for DNA CON-S env; Biological: Placebo for MVA-CMDR

Group 3: DNA Mosaic env and MVA-CMDR

EXPERIMENTAL

Participants will receive a single injection of DNA Mosaic env at Months 0, 1, and 2. They will receive a single injection of MVA-CMDR at Months 4 and 8.

Biological: DNA Mosaic env; Biological: MVA-CMDR

Group 3: Placebo vaccines for DNA Mosaic env and MVA-CMDR

PLACEBO COMPARATOR

Participants will receive a single injection of placebo for DNA Mosaic env at Months 0, 1, and 2. They will receive a single injection of placebo for MVA-CMDR at Months 4 and 8.

Biological: Placebo for DNA Mosaic env; Biological: Placebo for MVA-CMDR

Interventions

DNA Nat-B env BIOLOGICAL

4 mg to be administered as 1 mL intramuscularly (IM) by Biojector 2000® or with a needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated)

Group 1: DNA Nat-B env and MVA-CMDR

DNA CON-S env BIOLOGICAL

4 mg to be administered as 1 mL IM by Biojector 2000® or with a needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated)

Group 2: DNA CON-S env and MVA-CMDR

DNA Mosaic env BIOLOGICAL

4 mg to be administered as 1 mL IM by Biojector 2000® or with a needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated)

Group 3: DNA Mosaic env and MVA-CMDR

MVA-CMDR BIOLOGICAL

1×10\^8 plaque forming units (pfu) to be administered as 1 mL IM in the deltoid muscle of the non-dominant arm (unless medically contraindicated)

Also known as: Modified Vaccinia Virus Ankara (MVA-CMDR)

Group 1: DNA Nat-B env and MVA-CMDR; Group 2: DNA CON-S env and MVA-CMDR; Group 3: DNA Mosaic env and MVA-CMDR

Placebo for DNA Nat-B env BIOLOGICAL

Sodium Chloride for Injection, 0.9% to be administered as 1 mL IM by Biojector 2000® or with a needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated)

Group 1: Placebo vaccines for DNA Nat-B env and MVA-CMDR

Placebo for DNA CON-S env BIOLOGICAL

Sodium Chloride for Injection, 0.9% to be administered as 1 mL IM by Biojector 2000® or with a needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated)

Group 2: Placebo vaccines for DNA CON-S env and MVA-CMDR

Placebo for DNA Mosaic env BIOLOGICAL

Sodium Chloride for Injection, 0.9% to be administered as 1 mL IM by Biojector 2000® or with a needle and syringe in the deltoid muscle of the non-dominant arm (unless medically contraindicated)

Group 3: Placebo vaccines for DNA Mosaic env and MVA-CMDR

Placebo for MVA-CMDR BIOLOGICAL

Sodium Chloride for Injection, 0.9% to be administered as 1 mL IM in the deltoid muscle of the non-dominant arm (unless medically contraindicated)

Group 1: Placebo vaccines for DNA Nat-B env and MVA-CMDR; Group 2: Placebo vaccines for DNA CON-S env and MVA-CMDR; Group 3: Placebo vaccines for DNA Mosaic env and MVA-CMDR

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• General and Demographic Criteria
• Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willingness to be followed for the planned duration of the study
• Ability and willingness to provide informed consent
• Assessment of understanding: participant demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
• Willing to be contacted annually after completion of scheduled clinic visits for a total of 3 years for U.S. participants (5 years for participants in Switzerland) following initial study injection
• Agrees not to enroll in another study of an investigational research agent
• Good general health as shown by medical history, physical exam, and screening laboratory tests
• HIV-Related Criteria
• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks and amenable to HIV risk reduction counseling
• Assessed by the clinic staff as being at "low risk" for HIV infection and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
• Hemogram/Complete Blood Count (CBC)
• Hemoglobin greater than or equal to 12.5 g/dL for participants who were born female, greater than or equal to 13.5 g/dL for participants who were born male
• White blood cell count equal to 3,300 to 12,000 cells/mm\^3
• Total lymphocyte count greater than or equal to 800 cells/mm\^3

You may not qualify if:

• General
• Blood products received within 120 days before first vaccination
• Investigational research agents received within 30 days before first vaccination
• Body mass index (BMI) greater than or equal to 40
• Intent to participate in another study of an investigational research agent during the planned duration of the HVTN 106 study
• Pregnant or breastfeeding
• Vaccines and Other Injections
• Smallpox vaccine received within the last 5 years
• HIV vaccine(s) received in a prior HIV vaccine trial. For participants who have received control/placebo in an HIV vaccine trial, the HVTN 106 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis and the identity of the study control/placebo must be obtained.
• Non-HIV experimental vaccine(s) received within the last 5 years in a prior vaccine trial. Exceptions may be made for vaccines that have subsequently undergone licensure by the FDA. For participants who have received control/placebo in an experimental vaccine trial, the HVTN 106 PSRT will determine eligibility on a case-by-case basis. For participants who have received an experimental vaccine(s) more than 5 years ago, eligibility for enrollment will be determined by the HVTN 106 PSRT on a case-by-case basis.
• Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
• Influenza vaccine or any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (e.g., tetanus, pneumococcal, hepatitis A or B)
• Allergy treatment with antigen injections within 30 days before first vaccination or that are scheduled within 14 days after first vaccination
• Immune System
• Immunosuppressive medications received within 168 days before first vaccination. (Not excluded: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; \[3\] topical corticosteroids for mild, uncomplicated dermatitis; or \[4\] a single course of oral/parenteral corticosteroids at doses less than 2 mg/kg/day and length of therapy less than 11 days with completion at least 30 days prior to enrollment

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• CHAVI: collaborator
• IPPOX Foundation: collaborator
• MHRP: collaborator
• HIV Vaccine Trials Network: collaborator

Study Sites (7)

Alabama CRS

Birmingham, Alabama, 35294, United States

Location

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, 30030, United States

Location

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

Boston, Massachusetts, 02115-6110, United States

Location

Fenway Health (FH) CRS

Boston, Massachusetts, 02215-4302, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

Lausanne Vaccine and Immunotherapy Center CRS

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Related Publications (3)

• Moodie Z, Li SS, Giorgi EE, Williams LD, Dintwe O, Carpp LN, Chen S, Seaton KE, Sawant SS, Zhang L, Heptinstall J, Liu S, Grunenberg N, Tomaka F, Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Ake JA, Vasan S, Pantaleo G, Frank I, Baden LR, Goepfert PA, Keefer M, Chirenje M, Hosseinipour MC, Mngadi K, Laher F, Garrett N, Bekker LG, De Rosa S, Andersen-Nissen E, Kublin JG, Lu S, Gilbert PB, Gray GE, Corey L, McElrath MJ, Tomaras GD. A polyvalent DNA prime with matched polyvalent protein/GLA-SE boost regimen elicited the most robust and broad IgG and IgG3 V1V2 binding antibody and CD4+ T cell responses among 13 HIV vaccine trials. Emerg Microbes Infect. 2025 Dec;14(1):2485317. doi: 10.1080/22221751.2025.2485317. Epub 2025 Apr 7.

  PMID: 40190112 DERIVED

• Cohen KW, Fiore-Gartland A, Walsh SR, Yusim K, Frahm N, Elizaga ML, Maenza J, Scott H, Mayer KH, Goepfert PA, Edupuganti S, Pantaleo G, Hutter J, Morris DE, De Rosa SC, Geraghty DE, Robb ML, Michael NL, Fischer W, Giorgi EE, Malhi H, Pensiero MN, Ferrari G, Tomaras GD, Montefiori DC, Gilbert PB, McElrath MJ, Haynes BF, Korber BT, Baden LR; NIAID HVTN 106 Study Group. Trivalent mosaic or consensus HIV immunogens prime humoral and broader cellular immune responses in adults. J Clin Invest. 2023 Feb 15;133(4):e163338. doi: 10.1172/JCI163338.

  PMID: 36787249 DERIVED

• Campion SL, Brenna E, Thomson E, Fischer W, Ladell K, McLaren JE, Price DA, Frahm N, McElrath JM, Cohen KW, Maenza JR, Walsh SR, Baden LR, Haynes BF, Korber B, Borrow P, McMichael AJ. Preexisting memory CD4+ T cells contribute to the primary response in an HIV-1 vaccine trial. J Clin Invest. 2021 Dec 1;131(23):e150823. doi: 10.1172/JCI150823.

  PMID: 34850742 DERIVED

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Lindsey Baden

  Brigham and Women's Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2014
• First Posted: November 20, 2014
• Study Start: December 1, 2014
• Primary Completion: November 1, 2016
• Study Completion: July 6, 2020
• Last Updated: April 24, 2023

Record last verified: 2023-04

Locations

CH (1); US (6)