search
Back to results

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

Primary Purpose

Influenza, HIV, Tuberculosis

Status
Completed
Phase
Phase 4
Locations
South Africa
Study Type
Interventional
Intervention
Trivalent Inactivated Influenza Vaccine
Sponsored by
University of Witwatersrand, South Africa
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Influenza focused on measuring Tuberculosis, HIV infection, Immune responses to Influenza vaccination

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

  • Respiratory and Meningeal Pathogens research unit

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

TIV

Arm Description

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)

Outcomes

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.
• 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.
• 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.

Full Information

First Posted
February 21, 2013
Last Updated
September 3, 2018
Sponsor
University of Witwatersrand, South Africa
search

1. Study Identification

Unique Protocol Identification Number
NCT01811823
Brief Title
Effect of HIV and/or Active Tuberculosis on the Immune Responses to Trivalent Influenza Vaccine (TIV) in Adults
Acronym
TIV_HIV_TB
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2018
Overall Recruitment Status
Completed
Study Start Date
March 31, 2014 (Actual)
Primary Completion Date
November 20, 2014 (Actual)
Study Completion Date
November 20, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Witwatersrand, South Africa

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza, HIV, Tuberculosis
Keywords
Tuberculosis, HIV infection, Immune responses to Influenza vaccination

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
301 (Actual)

8. Arms, Groups, and Interventions

Arm Title
TIV
Arm Type
Other
Arm Description
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)
Intervention Type
Biological
Intervention Name(s)
Trivalent Inactivated Influenza Vaccine
Other Intervention Name(s)
Vaxigrip
Intervention Description
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)
Primary Outcome Measure Information:
Title
humoral antibody responses, measured by hemagglutinin inhibition assay (HAI), to each of three strains included in the seasonal non-adjuvanted trivalent influenza vaccine.
Description
• 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.
Time Frame
up to 6 weeks after end of the influenza season
Secondary Outcome Measure Information:
Title
• 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.
Description
• 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.
Time Frame
up to 6 weeks after the end of the influenza season

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
55 Years
Accepts Healthy Volunteers
No
Eligibility 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Shabir A Madhi, PHD
Organizational Affiliation
University of Witwatersrand, South Africa
Official's Role
Principal Investigator
Facility Information:
Facility Name
Respiratory and Meningeal Pathogens research unit
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2013
Country
South Africa

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs