Antigenic Competition in HIV Preventive Vaccines

NCT01159990 | Completed Phase 1

• 2 other identifiers: HVTN 08410785
• Study Type: interventional
• Target: 100
• Locations: 4 countries
• Sites: 7

Brief Summary

HIV vaccines are designed to create an immune response to certain components of the HIV virus called peptides. Previous research indicates that one peptide, called Gag, may be particularly important for stimulating an immune response to HIV. Many vaccines being studied combine multiple peptides, but including other peptides may weaken the body's response to Gag. This study will test whether a vaccine that targets Gag and another peptide called Env is better than a vaccine without Env at causing an immune response to Gag.

Conditions

HIV Infections

Keywords

HIV Preventive Vaccine; HIV Seronegativity

Outcome Measures

Primary Outcomes (2)

• Magnitude of Gag and/or Pol-specific T-cell responses, as measured by Enzyme-Linked Immunospot (ELISpot)

  Measured 4 weeks after immunization

• Number of Gag and/or Pol epitopes targeted by CD4+ and CD8+ T-cells, as measured by ELISpot

  Measured 4 weeks after immunization

Secondary Outcomes (3)

• Number of individuals mounting T-cell responses to Gag and/or Pol, as assessed by ELISpot

  Measured 4 weeks after immunization

• Local and systemic reactogenicity signs and symptoms, laboratory measures of safety, adverse events (AEs), and AEs reported on an expedited basis to Division of AIDS (DAIDS)

  Measured over 6 months after immunization

• Magnitude of Gag and/or Pol-specific CD4+ and CD8+ T-cell responses, as measured by intracellular cytokine staining (ICS)

  Measured 4 weeks after immunization

Study Arms (2)

Recombinant adenovirus serotype 5 (rAd5) Gag/Pol Env A/B/C

EXPERIMENTAL

Participants will receive one intramuscular injection of rAd5 Gag/Pol Env A/B/C.

Biological: rAd5 Gag-Pol Env A/B/C

rAd5 gag/pol

ACTIVE COMPARATOR

Participants will receive one intramuscular injection of rAd5 gag/pol.

Biological: rAd5 Gag-Pol

Interventions

rAd5 Gag-Pol Env A/B/C BIOLOGICAL

1×10\^10 particle units (PU) rAd5 Gag-Pol, Env A/B/C (3:1:1:1 mixture) delivered via intramuscular injection

Recombinant adenovirus serotype 5 (rAd5) Gag/Pol Env A/B/C

rAd5 Gag-Pol BIOLOGICAL

5×10\^9 PU rAd5 Gag-Pol delivered via intramuscular injection

rAd5 gag/pol

Eligibility Criteria

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

You may qualify if:

• 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
• Completes a questionnaire prior to vaccination that demonstrates an understanding of this study and that in a previous trial there was an association of increased HIV acquisition with receipt of that study vaccine
• Willingness to receive HIV test results
• Willingness to discuss HIV infection risks, amenable to HIV risk reduction counseling, and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
• Willingness to continue annual follow-up contact after the last required protocol clinic visit, for a total of 5 years following enrollment
• Good general health as shown by medical history, physical exam, and screening laboratory tests
• Assessed by the clinic staff as being at low risk for HIV infection on the basis of sexual behaviors within the 12 months prior to enrollment
• Adenovirus 5 (Ad5) neutralizing antibody (nAb) titer less than 1:18
• Hemoglobin greater than or equal to 11.0 g/dL for volunteers who were born female, or greater than or equal to 13.0 g/dL for volunteers who were born male
• White blood cell (WBC) count between 3,300 and 12,000 cells/mm3
• Total lymphocyte count greater than or equal to 800 cells/mm3
• Remaining differential either within institutional normal range or with site physician approval
• Platelet count between 125,000 and 550,000/mm3
• Alanine aminotransferase (ALT) less than or equal to 1.25 times institutional upper limits of normal
• Negative HIV-1 and HIV-2 blood test: U.S. participants must have negative FDA-approved enzyme immunoassay (EIA). Non-U.S. sites may use locally available assays that have been approved by HVTN laboratory operations.

You may not qualify if:

• Within the 12 months prior to enrollment: excessive daily alcohol use, frequent binge drinking, chronic marijuana abuse, or any other use of illicit drugs
• Within the 12 months prior to enrollment: a history of newly acquired syphilis, gonorrhea, non-gonococcal urethritis, herpes simplex virus type 2 (HSV2), Chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B virus
• Received non-HIV experimental vaccine(s) 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 potential participants who have received the control or placebo in an experimental vaccine trial, the HVTN 084 PSRT will determine eligibility on a case-by-case basis.
• For potential participants who received the control or placebo in an HIV vaccine trial, documentation of the identity of the study control or placebo must be provided to the HVTN 084 protocol safety review team (PSRT), who will determine eligibility on a case-by-case basis.
• Serious adverse reactions to vaccines including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, or abdominal pain. A participant who had a nonanaphylactic adverse reaction to pertussis vaccine as a child will not be excluded.
• Immunosuppressive medications received within 168 days before first vaccination, except (1) corticosteroid nasal spray for allergic rhinitis, (2) topical corticosteroids for mild, uncomplicated dermatitis, or (3) oral or parenteral corticosteroids given for non-chronic conditions not expected to recur (length of therapy 10 days or less with completion at least 30 days prior to enrollment).
• Blood products received within 120 days before first vaccination
• Immunoglobulin received within 60 days before first vaccination
• Live attenuated vaccines other than influenza vaccine received within 30 days before vaccination or scheduled within 14 days after injection (e.g., measles, mumps, and rubella \[MMR\]; oral polio vaccine \[OPV\]; varicella; yellow fever)
• Influenza vaccines or any vaccines that are not live attenuated vaccines (e.g., tetanus, pneumococcal, hepatitis A or B), or allergy treatment with antigen injections that were received within 14 days prior to the vaccination
• Investigational research agents received within 30 days before first vaccination
• Intent to participate in another study of an investigational research agent during the planned duration of the study
• Current anti-tuberculosis (TB) prophylaxis or therapy
• Clinically significant medical condition, physical examination findings, abnormal laboratory results, or past medical history with implications for current health.
• Any medical, psychiatric, occupational, or other condition that, in the judgment of the investigator, would interfere with or serve as a contraindication to protocol adherence, assessment of safety or reactogenicity, or a participant's ability to give informed consent

Sponsors & Collaborators

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

Study Sites (7)

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

Boston, Massachusetts, 02115-6110, 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

Sao Paulo HVTU - CRT DST/AIDS CRS

São Paulo, 04121-000, Brazil

Location

ACSA CRS

Iquitos, Maynas, 1, Peru

Location

Barranco CRS

Lima, 04, Peru

Location

Lausanne Vaccine and Immunotherapy Center CRS

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Related Publications (2)

• McElrath MJ, De Rosa SC, Moodie Z, Dubey S, Kierstead L, Janes H, Defawe OD, Carter DK, Hural J, Akondy R, Buchbinder SP, Robertson MN, Mehrotra DV, Self SG, Corey L, Shiver JW, Casimiro DR; Step Study Protocol Team. HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet. 2008 Nov 29;372(9653):1894-1905. doi: 10.1016/S0140-6736(08)61592-5. Epub 2008 Nov 13.

  PMID: 19012957 BACKGROUND

• Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, Moodley E, Reddy S, de Pierres C, Mncube Z, Mkhwanazi N, Bishop K, van der Stok M, Nair K, Khan N, Crawford H, Payne R, Leslie A, Prado J, Prendergast A, Frater J, McCarthy N, Brander C, Learn GH, Nickle D, Rousseau C, Coovadia H, Mullins JI, Heckerman D, Walker BD, Goulder P. CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med. 2007 Jan;13(1):46-53. doi: 10.1038/nm1520. Epub 2006 Dec 17.

  PMID: 17173051 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

• Esper Kallas, MD, PhD

  University of Sao Paulo

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: July 8, 2010
• First Posted: July 12, 2010
• Study Start: January 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: April 6, 2017
• Last Updated: October 15, 2021

Record last verified: 2021-10

Locations

PE (2); US (3); CH (1); BR (1)