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

Study Overview
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Brief Summary
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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

Official Title
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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

Conditions
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Influenza, HIV, Tuberculosis

Intervention / Treatment
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* Biological: Trivalent Inactivated Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: TIV<br>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<br>* 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)<br>* Other names: Vaxigrip;|

What is the study measuring?
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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. | • 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. | • 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Tuberculosis, HIV infection, Immune responses to Influenza vaccination