Evaluating the Safety and Immune Response to Different Combinations of the DNA-HIV-PT123 and AIDSVAX® B/E Vaccines in Healthy, HIV-Uninfected Adults

NCT02207920 | Completed Phase 1 DMC

• 2 other identifiers: HVTN 10511986
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 7

Brief Summary

This study will evaluate the safety, tolerability, and immune response to different combinations of two experimental HIV vaccines-the DNA-HIV-PT123 vaccine and the AIDSVAX® B/E vaccine-in healthy adults who are not infected with HIV.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (9)

• Frequency of local and systemic reactogenicity signs and symptoms

  Measured through Month 12

• Laboratory measure of safety: measurement of complete blood count (CBC)

  Including differential and platelets

  Measured through Month 12

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

  Measured through Month 12

• Laboratory measure of safety: measurement of creatinine

  Measured through Month 12

• Frequency of adverse events (AEs)

  Measured through Month 12

• Frequency of serious adverse events (SAEs)

  Measured through Month 12

• HIV-specific binding antibody (Ab) response as assessed by binding Ab multiplex assay

  Measured 2 weeks after the 4th vaccination

• Response rate and magnitude of CD4 T cell responses as assessed by intracellular cytokine staining (ICS) assays

  Measured 2 weeks after the 4th vaccination

• Response rate and magnitude of CD8 T cell responses as assessed by ICS assays

  Measured 2 weeks after the 4th vaccination

Secondary Outcomes (2)

• Neutralizing antibody (nAb) magnitude and breadth against tier 1 and tier 2 HIV-1 isolates as assessed by area under the magnitude-breadth curves

  Measured 2 weeks after the 4th vaccination

• Measurement of HIV-specific Ab and T-cell responses

  Measured 6 months after the 4th vaccination

Study Arms (4)

Group 1

EXPERIMENTAL

At study entry and Month 1, participants will receive placebo for DNA-HIV-PT123 in their left deltoid and AIDSVAX B/E in their right deltoid. At Months 3 and 6, participants will receive DNA-HIV-PT123 in their left deltoid and placebo for AIDSVAX B/E in their right deltoid.

Biological: AIDSVAX B/E Vaccine; Biological: DNA-HIV-PT123 Vaccine; Biological: Placebo for DNA-HIV-PT123; Biological: Placebo for AIDSVAX B/E

Group 2

EXPERIMENTAL

At study entry and Month 1, participants will receive DNA-HIV-PT123 in their left deltoid and placebo for AIDSVAX B/E in their right deltoid. At Months 3 and 6, participants will receive placebo for DNA-HIV-PT123 in their left deltoid and AIDSVAX B/E in their right deltoid.

Biological: AIDSVAX B/E Vaccine; Biological: DNA-HIV-PT123 Vaccine; Biological: Placebo for DNA-HIV-PT123; Biological: Placebo for AIDSVAX B/E

Group 3

EXPERIMENTAL

At study entry and Month 1, participants will receive DNA-HIV-PT123 in their left deltoid and placebo for AIDSVAX B/E in their right deltoid. At Months 3 and 6, participants will receive DNA-HIV-PT123 in their left deltoid and AIDSVAX B/E in their right deltoid.

Biological: AIDSVAX B/E Vaccine; Biological: DNA-HIV-PT123 Vaccine; Biological: Placebo for AIDSVAX B/E

Group 4

EXPERIMENTAL

At study entry and Months 1, 3, and 6, participants will receive DNA-HIV-PT123 in their left deltoid and AIDSVAX B/E in their right deltoid.

Biological: AIDSVAX B/E Vaccine; Biological: DNA-HIV-PT123 Vaccine

Interventions

AIDSVAX B/E Vaccine BIOLOGICAL

600 mcg/mL to be administered as 1 mL intramuscular (IM) injection

Group 1; Group 2; Group 3; Group 4

DNA-HIV-PT123 Vaccine BIOLOGICAL

4 mg/mL to be administered as 1 mL IM injection

Group 1; Group 2; Group 3; Group 4

Placebo for DNA-HIV-PT123 BIOLOGICAL

Sodium chloride for injection USP, 0.9%; administered as 1 mL IM injection

Group 1; Group 2

Placebo for AIDSVAX B/E BIOLOGICAL

Sodium chloride for injection USP, 0.9%; administered as 1 mL IM injection

Group 1; Group 2; Group 3

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
• Agrees not to enroll in another study of an investigational research agent before the last required protocol clinic visit
• 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 11.0 g/dL for participants who were born female; greater than or equal to 13.0 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
• Remaining differential either within institutional normal range or with site physician approval

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; or BMI greater than or equal to 35 with 2 or more of the following: age greater than 45, systolic blood pressure greater than 140 mm Hg, diastolic blood pressure greater than 90 mm Hg, or known hyperlipidemia
• Intent to participate in another study of an investigational research agent before the last required protocol clinic visit
• Pregnant or breastfeeding
• Vaccines and Other Injections
• HIV vaccine(s) received in a prior HIV vaccine trial. For participants who have received control/placebo in an HIV vaccine trial, the HVTN 105 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis.
• 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 FDA. For participants who have received control/placebo in an experimental vaccine trial, the HVTN 105 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 105 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)
• Serious adverse reactions to vaccines, including history of anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not excluded: a participant who had a nonanaphylactic adverse reaction to pertussis vaccine as a child)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (7)

Bridge HIV CRS

San Francisco, California, 94143, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

New York Blood Center CRS

New York, New York, 10065, United States

Location

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, 14642, United States

Location

Penn Prevention CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, 37232-2582, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98109-1024, United States

Location

Related Publications (5)

• 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

• Basu M, Fucile C, Piepenbrink MS, Bunce CA, Man LX, Liesveld J, Rosenberg AF, Keefer MC, Kobie JJ. Mixed Origins: HIV gp120-Specific Memory Develops from Pre-Existing Memory and Naive B Cells Following Vaccination in Humans. AIDS Res Hum Retroviruses. 2023 Jul;39(7):350-366. doi: 10.1089/AID.2022.0104. Epub 2023 Mar 22.

  PMID: 36762930 DERIVED

• Fischinger S, Cizmeci D, Deng D, Grant SP, Frahm N, McElrath J, Fuchs J, Bart PA, Pantaleo G, Keefer M, O Hahn W, Rouphael N, Churchyard G, Moodie Z, Donastorg Y, Streeck H, Alter G. Sequence and vector shapes vaccine induced antibody effector functions in HIV vaccine trials. PLoS Pathog. 2021 Nov 29;17(11):e1010016. doi: 10.1371/journal.ppat.1010016. eCollection 2021 Nov.

  PMID: 34843602 DERIVED

• Basu M, Piepenbrink MS, Francois C, Roche F, Zheng B, Spencer DA, Hessell AJ, Fucile CF, Rosenberg AF, Bunce CA, Liesveld J, Keefer MC, Kobie JJ. Persistence of HIV-1 Env-Specific Plasmablast Lineages in Plasma Cells after Vaccination in Humans. Cell Rep Med. 2020 May 19;1(2):100015. doi: 10.1016/j.xcrm.2020.100015.

  PMID: 32577626 DERIVED

• Rouphael NG, Morgan C, Li SS, Jensen R, Sanchez B, Karuna S, Swann E, Sobieszczyk ME, Frank I, Wilson GJ, Tieu HV, Maenza J, Norwood A, Kobie J, Sinangil F, Pantaleo G, Ding S, McElrath MJ, De Rosa SC, Montefiori DC, Ferrari G, Tomaras GD, Keefer MC; HVTN 105 Protocol Team and the NIAID HIV Vaccine Trials Network. DNA priming and gp120 boosting induces HIV-specific antibodies in a randomized clinical trial. J Clin Invest. 2019 Nov 1;129(11):4769-4785. doi: 10.1172/JCI128699.

  PMID: 31566579 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

AIDSVAX B-E

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

• Michael Keefer

  University of Rochester

  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: July 31, 2014
• First Posted: August 4, 2014
• Study Start: July 1, 2014
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2015
• Last Updated: October 15, 2021

Record last verified: 2021-10

Locations

US (7)