Effect of HIV and/or Active Tuberculosis on the Immune Responses to Trivalent Influenza Vaccine (TIV) in Adults (TIV_HIV_TB)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Witwatersrand, South Africa
Sponsor:
Information provided by (Responsible Party):
Michelle Groome, University of Witwatersrand, South Africa
ClinicalTrials.gov Identifier:
NCT01811823
First received: February 21, 2013
Last updated: August 11, 2014
Last verified: August 2014
  Purpose

Prospective, open-labelled study which will enrol 360 participants in four groups of 80 participants including: HIV-uninfected adults without evidence of TB; HIV-infected adults without any evidence of TB; HIV-uninfected adults with concurrent microbiologic confirmed TB, HIV-infected adults with concurrent microbiologic confirmed TB.

Participants will receive the recommended seasonal 2013 un-adjuvanted Trivalent Influenza Vaccine (TIV). At 3 visits, blood will be collected for determination of immune responses.

Objective:

• To determine the effect of HIV-infection, tuberculosis (TB) and HIV-TB co-infection on immune responses


Condition Intervention Phase
Influenza
HIV
Tuberculosis
Biological: Trivalent Inactivated Influenza Vaccine
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effect of HIV and/or Active Tuberculosis on the Humoral and Cell Mediated Immune Responses to Un-adjuvanted Trivalent Sub-unit Influenza Vaccine (TIV) in Adults

Resource links provided by NLM:


Further study details as provided by University of Witwatersrand, South Africa:

Primary Outcome Measures:
  • humoral antibody responses, measured by hemagglutinin inhibition assay (HAI), to each of three strains included in the seasonal non-adjuvanted trivalent influenza vaccine. [ Time Frame: up to 6 weeks after end of the influenza season ] [ Designated as safety issue: No ]
    • To determine the effect of HIV-infection, tuberculosis (TB) and HIV-TB co-infection on humoral antibody responses, measured by hemagglutinin inhibition assay (HAI), to each of three strains included in the seasonal non-adjuvanted trivalent influenza vaccine In this study we will use the following definitions to assess the humoral immune response to TIV: HAI titers <1:10 = seronegative; HAI titers ≥1:10 = seropositive; HAI titers ≥1:40 = sero-protective; sero-response rate (primary outcome measure) will be defined as a titer of ≥1:40 in an individual with baseline titers of <1:10, or >4-fold increase of HAI titers if baseline titers were ≥1:10. Hemagglutination inhibition assays will be performed on serum as per recommended methods. Sera will be titrated against antigens from the influenza vaccine strains included in the 2013 seasonal TIV.


Secondary Outcome Measures:
  • • To compare the effect of HIV-infection, tuberculosis (TB) and HIV-TB co-infection on vaccine-strain specific cell mediated immune responses, evaluated by ELISPOT assay, following non-adjuvanted TIV vaccination. [ Time Frame: up to 6 weeks after the end of the influenza season ] [ Designated as safety issue: No ]

    • To compare the effect of HIV-infection, tuberculosis (TB) and HIV-TB co-infection on vaccine-strain specific cell mediated immune responses, evaluated by Enzyme-linked immunosorbent spot (ELISPOT) assay, following non-adjuvanted TIV vaccination.

    The cell mediated Immunity (CMI) evaluations in this study will provide novel information on influenza-specific CMI in individuals with TB. Interferon gama- ELISPOT responses will be assessed on fresh Peripheral Blood Mononuclear Cells (PBMCs). Spots will be visualized with a ELISPOT plate reader. Background (non-specific) spots detected in the medium-containing wells will be subtracted from the wells stimulated with influenza antigens. Results will be reported as Spot forming cell (SFC)/106 PBMCs.



Estimated Enrollment: 360
Study Start Date: March 2014
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
TIV

Trivalent Inactivated Influenza Vaccine The study vaccine will be the seasonal 2013 un-adjuvanted TIV which is provided as a 0•5 milliliter suspension of split virus mixture of 15 micrograms each of circulating H1N1- like strain, H3N2- like strain and B - like strain.

The WHO recommended vaccine formulation for Southern Hemisphere 2013 Influenza Season contains the following influenza strains:

  • A/California/7/2009 (H1N1)pdm-like virus
  • A/Victoria/361/2011 (H3N2)-like virus
  • B/Wisconsin/1/2010-like virus. (Yamagata lineage)
Biological: Trivalent Inactivated Influenza Vaccine

The study vaccine will be the seasonal 2013 un-adjuvanted TIV which is provided as a 0•5 milliliter suspension of split virus mixture of 15 micrograms each of circulating H1N1- like strain, H3N2- like strain and B - like strain.

The WHO recommended vaccine formulation for Southern Hemisphere 2013 Influenza Season contains the following influenza strains:

  • A/California/7/2009 (H1N1)pdm-like virus
  • A/Victoria/361/2011 (H3N2)-like virus
  • B/Wisconsin/1/2010-like virus. (Yamagata lineage)
Other Name: Vaxigrip

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • for HIV-infected subjects: a Cluster of Differntiation4 (CD4+) cell count of >100/ul within the previous 3 months;
  • able to attend the clinic for immunogenicity and illness visits;
  • for subjects with TB: having a microbiologic confirmed diagnosis of TB (defined as the presence of acid-fast-bacilli (AFB) on a sputum smear or other specimen and/or a positive culture for M. tuberculosis) within the past 120 days;
  • Aged 18 to 55 years.

Exclusion Criteria:

  • any contraindication to influenza vaccine;
  • any contraindication to intramuscular injections;
  • any existing grade 3 or grade 4 laboratory or clinical toxicity as per Division of Acquired Immune Deficiency Syndrome (DAIDS) toxicity tables;
  • systemic steroid treatment for >21 days within the past 30 days.
  • pregnancy (a urine Human Chorionic Gonadotropin (βHCG) will be performed on all women of childbearing age to exclude pregnancy)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01811823

Locations
South Africa
Respiratory and Meningeal Pathogens research unit Recruiting
Soweto, Johannesburg, Gauteng, South Africa, 2013
Contact: Clare L Cutland, MBBCH       cutlandc@rmpru.co.za   
Sub-Investigator: Stephanie Jones, MD         
Sub-Investigator: Anthonet L Koen, MD         
Sub-Investigator: Clare L Cutland, MD         
Sub-Investigator: Niresha Govender, MD         
Sub-Investigator: Lisa Jose, MD         
Sub-Investigator: Razia Hassan Moosa, MBBCH, MPH         
Sponsors and Collaborators
University of Witwatersrand, South Africa
Investigators
Principal Investigator: Shabir A Madhi, PHD University of the Witwatersrand
  More Information

No publications provided

Responsible Party: Michelle Groome, Dr, University of Witwatersrand, South Africa
ClinicalTrials.gov Identifier: NCT01811823     History of Changes
Other Study ID Numbers: TIV_HIV_TB
Study First Received: February 21, 2013
Last Updated: August 11, 2014
Health Authority: South Africa: Human Research Ethics Committee

Keywords provided by University of Witwatersrand, South Africa:
Tuberculosis
HIV infection
Immune responses to Influenza vaccination

Additional relevant MeSH terms:
Influenza, Human
Tuberculosis
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections

ClinicalTrials.gov processed this record on August 26, 2014