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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Biological: rAd35; Biological: rAd5; Biological: rAd35 placebo; Biological: rAd5 placebo; Biological: DNA Vaccine; Biological: DNA Vaccine placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 192
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Alabama CRS
  • California
    • San Francisco, California, United States, 94143
      • Bridge HIV CRS
  • Georgia
    • Decatur, Georgia, United States, 30030
      • The Hope Clinic of the Emory Vaccine Center CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02215-4302
      • Fenway Health (FH) CRS
    • Boston, Massachusetts, United States, 02115-6110
      • Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
  • New York
    • New York, New York, United States, 10065
      • New York Blood Center CRS
    • New York, New York, United States, 10032-3732
      • Columbia P&S CRS
    • Rochester, New York, United States, 14642
      • University of Rochester Vaccines to Prevent HIV Infection CRS
  • Tennessee
    • Nashville, Tennessee, United States, 37232-2582
      • Vanderbilt Vaccine (VV) CRS
  • Washington
    • Seattle, Washington, United States, 98109-1024
      • Seattle Vaccine and Prevention CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1A; rAD5-naive participants will receive rAd35 intramuscularly at study entry and rAd5 intramuscularly at Month 6	Biological: rAd35; VRC-HIVADV027-00-VP 1 x 10^10 PU administered as 1 mL; Biological: rAd5; 4 mg VRC-HIVADV038-00-VP administered as 1 mL
Placebo Comparator: 1B; Participants will receive rAd35 placebo intramuscularly at study entry and rAd5 placebo intramuscularly at Month 6	Biological: rAd35 placebo; 1 mL VRC-PBSPLA043-00-0VP; Biological: rAd5 placebo; 1 mL VRC-DILUENT013-DIL-VP
Experimental: 2A; rAD5-naive participants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd5 intramuscularly at Month 6	Biological: rAd5; 4 mg VRC-HIVADV038-00-VP administered as 1 mL; Biological: DNA Vaccine; 4 mg VRC-HIVDNA044-00-VP administered as 1 mL
Placebo Comparator: 2B; Participants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd5 placebo intramuscularly at Month 6	Biological: rAd5 placebo; 1 mL VRC-DILUENT013-DIL-VP; Biological: DNA Vaccine placebo; 1 mL VRC-PBSPLA043-00-VP
Experimental: 3A; Participants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd35 intramuscularly at Month 6	Biological: rAd35; VRC-HIVADV027-00-VP 1 x 10^10 PU administered as 1 mL; Biological: DNA Vaccine; 4 mg VRC-HIVDNA044-00-VP administered as 1 mL
Placebo Comparator: 3B; Participants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd35 placebo intramuscularly at Month 6	Biological: rAd35 placebo; 1 mL VRC-PBSPLA043-00-0VP; Biological: DNA Vaccine placebo; 1 mL VRC-PBSPLA043-00-VP
Experimental: 4A; Participants will receive DNA vaccine intramuscularly at study entry and Months 1 and 2 and rAd35 intramuscularly at Month 6	Biological: rAd35; VRC-HIVADV027-00-VP 1 x 10^10 PU administered as 1 mL; Biological: DNA Vaccine; 4 mg VRC-HIVDNA044-00-VP administered as 1 mL
Placebo Comparator: 4B; Participants will receive DNA vaccine placebo intramuscularly at study entry and Months 1 and 2 and rAd35 placebo intramuscularly at Month 6	Biological: rAd35 placebo; 1 mL VRC-PBSPLA043-00-0VP; Biological: DNA Vaccine placebo; 1 mL VRC-PBSPLA043-00-VP

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Local and systemic reactogenicity signs and symptoms, laboratory measures of safety, and adverse and expedited adverse events	Throughout study
Magnitude and frequency of immune responses between HIV-1 clade A env rAD35 and rAd5 vaccines when given as a boost after DNA vaccine	At Week 4 following the fourth vaccination
Magnitude and frequency of immune responses between clade A env rAD35 vaccine primed by Ad35 versus DNA	At Week 4 following the last vaccination
Magnitude and frequency of immune responses of HIV-1 clade A env rAD35 vaccine when given as a boost	At Week 4 following the fourth vaccination

Secondary Outcome Measures

Outcome Measure	Time Frame
Immunogenicity of HIV-1 clade A env rAD35 vaccine given as a prime	At Week 4 following the first vaccination

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: HIV Vaccine Trials Network
• Investigators: Study Chair: Jonathan Fuchs, MD, MPH, SFDPH/UCSF; Study Chair: Pierre-Alexandre Bart, MD, CHUV (Lausanne)

Publications and helpful links

General Publications

• 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.
• Priddy FH, Brown D, Kublin J, Monahan K, Wright DP, Lalezari J, Santiago S, Marmor M, Lally M, Novak RM, Brown SJ, Kulkarni P, Dubey SA, Kierstead LS, Casimiro DR, Mogg R, DiNubile MJ, Shiver JW, Leavitt RY, Robertson MN, Mehrotra DV, Quirk E; Merck V520-016 Study Group. Safety and immunogenicity of a replication-incompetent adenovirus type 5 HIV-1 clade B gag/pol/nef vaccine in healthy adults. Clin Infect Dis. 2008 Jun 1;46(11):1769-81. doi: 10.1086/587993.
• Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, Gilbert PB, Lama JR, Marmor M, Del Rio C, McElrath MJ, Casimiro DR, Gottesdiener KM, Chodakewitz JA, Corey L, Robertson MN; Step Study Protocol Team. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet. 2008 Nov 29;372(9653):1881-1893. doi: 10.1016/S0140-6736(08)61591-3. Epub 2008 Nov 13.
• Sheets RL, Stein J, Bailer RT, Koup RA, Andrews C, Nason M, He B, Koo E, Trotter H, Duffy C, Manetz TS, Gomez P. Biodistribution and toxicological safety of adenovirus type 5 and type 35 vectored vaccines against human immunodeficiency virus-1 (HIV-1), Ebola, or Marburg are similar despite differing adenovirus serotype vector, manufacturer's construct, or gene inserts. J Immunotoxicol. 2008 Jul;5(3):315-35. doi: 10.1080/15376510802312464.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): February 1, 2011
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: December 2, 2008
• First Submitted That Met QC Criteria: December 2, 2008
• First Posted (Estimate): December 3, 2008

Study Record Updates

• Last Update Posted (Actual): October 14, 2021
• Last Update Submitted That Met QC Criteria: October 13, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: HIV Seronegativity; HIV Preventive Vaccine; Adenovirus
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: HVTN 077; 10702 (Registry Identifier: DAIDS ES Registry Number)