Examining the Role of Genetics in Determining the Immune Response to an HIV Vaccine in HIV-Uninfected Adult Twins

NCT01054872 | Completed Phase 1

• 2 other identifiers: HVTN 08210771
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to examine the role of genetics in determining the immune response to an HIV vaccine in pairs of HIV-uninfected twins.

Conditions

HIV Infections

Keywords

HIV Seronegativity; HIV Preventive Vaccine

Outcome Measures

Primary Outcomes (2)

• Magnitude of HIV-1 insert-specific cellular responses, as measured by ELISpot, intracellular cytokine staining (ICS), or other modalities

  Measured at 4 weeks after the rAd5 boost

• Magnitude of Ad-specific cellular responses, as measured by ELISpot, ICS, or other modalities

  Measured at 4 weeks after the rAd5 boost

Secondary Outcomes (9)

• Number of HIV epitopes targeted by CD4 and CD8 T-cells, as measured by ELISpot, ICS, or other modalities

  Measured at 4 weeks after the rAd5 boost

• Number of Ad epitopes targeted by CD4 and CD8 T-cells, as measured by ELISpot, ICS, or other modalities

  Measured at 4 weeks after the rAd5 boost

• Percentage of insert-specific T lymphocytes expressing 1, 2, or 3 cytokines, as measured by HIV-1 specific multi-parameter ICS or other modalities

  Measured at 4 weeks after the rAd5 boost

• Percentage of Ad-specific T lymphocytes expressing 1, 2, or 3 cytokines, as measured by HIV-1 specific multi-parameter ICS or other modalities

  Measured at 4 weeks after the rAd5 boost

• HIV-1-specific nAb titers, as measured by antibody titer assays

  Measured at 4 weeks after the rAd5 boost

Study Arms (2)

Monozygotic (MZ) Twins

EXPERIMENTAL

Participants will receive the DNA vaccine at baseline and Months 1 and 2. They will then receive the rAd5 vaccine at Month 6.

Biological: HIV-1 DNA plasmid vaccine; Biological: HIV-1 recombinant Ad5 vaccine

Dizygotic (DZ) Twins

EXPERIMENTAL

Participants will receive the DNA vaccine at baseline and Months 1 and 2. They will then receive the rAd5 vaccine at Month 6.

Biological: HIV-1 DNA plasmid vaccine; Biological: HIV-1 recombinant Ad5 vaccine

Interventions

HIV-1 DNA plasmid vaccine BIOLOGICAL

4 mg injection administered as 1 mL intramuscularly via Biojector in deltoid

Also known as: VRC-HIVDNA016-00-VP

Dizygotic (DZ) Twins; Monozygotic (MZ) Twins

HIV-1 recombinant Ad5 vaccine BIOLOGICAL

1 x 10\^10 particle units (PU) administered as 1 mL intramuscularly by needle and syringe in deltoid

Also known as: VRC-HIVADV014-00-VP

Dizygotic (DZ) Twins; Monozygotic (MZ) Twins

Eligibility Criteria

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

You may qualify if:

• Pairs of MZ and DZ twins who shared common childhood environments
• If born male, participant must be fully circumcised (as documented at screening examination). Circumcision must have been performed at least 90 days prior to first vaccination and surgical site must be fully healed.
• Access to a participating HIV Vaccine Trials Network (HVTN) clinical research site (CRS) and willing to be followed for the duration of the study
• Assessment of understanding, including the completion of a questionnaire before the first vaccination and demonstration of understanding for all questionnaire items answered incorrectly
• Willing to receive HIV test results
• Willing to discuss HIV infection risks, amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk HIV exposure through the last required study visit, and willing to continue annual follow-up contact after the final study visit for a total of 5 years after study entry
• In good general health, as shown by medical history, physical exam, and screening laboratory tests
• Assessed by the clinic staff as having a "low risk" for HIV infection on the basis of sexual behaviors in the 12 months before study entry. More information on this criterion can be found in the protocol.
• Ad5 nAb titer less than 1:18
• Hemoglobin greater than or equal to 11.3 g/dL for participants who were born female, and greater than or equal to 13.0 g/dL for participants who were born male
• White blood cell count between 3,300 to 12,000 cells/mm\^3
• Total lymphocyte count greater than or equal to 800 cells/mm\^3
• Remaining differential either within site's normal range or with site physician approval
• Platelet level between 125,000 to 550,000/mm\^3
• Alanine aminotransferase (ALT) less than or equal to 2.5 times the site's upper limit of normal

You may not qualify if:

• Excessive daily alcohol use, frequent binge drinking, chronic marijuana abuse, or use of any other illicit drugs in the 12 months before study entry
• History of newly acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus type 2, chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B in the 12 months before study entry
• Received HIV vaccines in a prior HIV vaccine trial
• Immunosuppressive medications received within 168 days before the first study vaccination
• Blood products received within 120 days before the first study vaccination
• Immunoglobulin received within 60 days before the first study vaccination
• Live attenuated vaccines received within 30 days before the first study vaccination or scheduled within 14 days after injection
• Investigational research agents received within 30 days before the first study vaccination
• Intent to participate in another investigational drug study
• Any vaccines that are not live attenuated vaccines or allergy treatment with antigen injections received within 14 days before the first study vaccination
• Current anti-tuberculosis preventive therapy or treatment
• Clinically significant medical condition, abnormal physical examination findings, abnormal laboratory results, or past medical history that may affect current health
• Any medical, psychiatric, occupational, or other condition that would interfere with participation in the study
• Serious adverse reactions to vaccines, including anaphylaxis and related symptoms (e.g., hives, respiratory difficulty, angioedema, abdominal pain). A person who had an adverse reaction to the pertussis vaccine as a child is not excluded.
• Autoimmune disease or immunodeficiency

Sponsors & Collaborators

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

Study Sites (2)

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

Boston, Massachusetts, 02115, United States

Location

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98104, United States

Location

Related Publications (2)

• Hunt PW, Carrington M. Host genetic determinants of HIV pathogenesis: an immunologic perspective. Curr Opin HIV AIDS. 2008 May;3(3):342-8. doi: 10.1097/COH.0b013e3282fbaa92.

  PMID: 19372988 BACKGROUND

• Newport MJ, Goetghebuer T, Marchant A. Hunting for immune response regulatory genes: vaccination studies in infant twins. Expert Rev Vaccines. 2005 Oct;4(5):739-46. doi: 10.1586/14760584.4.5.739.

  PMID: 16221074 BACKGROUND

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: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2010
• First Posted: January 22, 2010
• Study Start: January 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: June 1, 2016
• Last Updated: October 15, 2021

Record last verified: 2021-10

Locations

US (2)