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

September 3, 2018 updated by: Shabir Madhi, University of Witwatersrand, South Africa

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

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

301

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • South Africa
    • Gauteng
      • Johannesburg, Gauteng, South Africa, 2013
        • Respiratory and Meningeal Pathogens research unit

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: 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 Names:
  • Vaxigrip

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
• 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.
up to 6 weeks after end of the influenza season

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
• 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

• 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.
up to 6 weeks after the end of the influenza season

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Witwatersrand, South Africa

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

March 31, 2014

Primary Completion (ACTUAL)

November 20, 2014

Study Completion (ACTUAL)

November 20, 2014

Study Registration Dates

First Submitted

February 21, 2013

First Submitted That Met QC Criteria

March 12, 2013

First Posted (ESTIMATE)

March 15, 2013

Study Record Updates

Last Update Posted (ACTUAL)

September 5, 2018

Last Update Submitted That Met QC Criteria

September 3, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • TIV_HIV_TB

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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