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Immunogenicity and Safety of Trivalent Influenza Vaccine in Non-pregnant HIV-infected Women

Primary Purpose

Influenza, Human Immunodeficiency Virus

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 Influenza, Human Immunodeficiency Virus

Eligibility Criteria

18 Years - 39 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

(i) Documented to be HIV-1 infected on one assay used in the Prevention of Mother to Child Transmission (PMTCT)/ other program undertaken within 12 weeks of study enrolment.

  • Able to understand and comply with planned study procedures.
  • Provides written informed consent prior to initiation of study.
  • Not pregnant at time of enrolment (confirmed by urine testing). If pregnant in past year, participant must be at least 6 months post delivery at time of enrolment.
  • Women age ≥ 18 years to < 39 years.

Exclusion Criteria:

  • Receipt of TIV, other than through the study, during the current and previous two influenza seasons, documented by medical history or record.
  • Receipt of any live licensed vaccine ≤ 28 days or any other vaccine (except for tetanus toxoid vaccine) ≤ 14 days prior to study-vaccine.
  • Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or medication) ≤ 28 days prior to vaccination in this study, unless study approval is obtained.
  • Any significant (in the opinion of the site investigator) acute illness and/or oral temperature greater than or equal to 38 degrees C ≤ 24 hours prior to study entry.
  • Use of anti-cancer systemic chemotherapy or radiation therapy ≤ 48 weeks of study enrollment, or has immunosuppression as a result of an underlying illness or treatment.
  • Long term use of glucocorticoids, including oral or parenteral prednisone ≥ 20 mg/day or equivalent for more than 2 consecutive weeks (or 2 weeks total) ≤ 12 weeks of study entry, or high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) ≤ 12 weeks before study entry (nasal and topical steroids are allowed).
  • Receipt of immunoglobulin or other blood products (with exception of Rho D immune globulin) ≤ 12 weeks prior to enrollment in this study or is scheduled to receive immunoglobulin or other blood products.
  • Receipt of Interleukin 2, IFN, GMCSF or other immune mediators ≤ 12 weeks before enrollment.
  • Uncontrolled major psychiatric disorder.
  • History of a severe adverse reaction to previous TIV.
  • Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.

Sites / Locations

  • Nrf/Dst Vpd Rmpru

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Trivalent Inactivated Influenza Vaccine

Arm Description

Single dose, intramuscular injection from a pre-filled syringe WHO recommendation for influenza vaccines for 2013 for the Southern-hemisphere included the following vaccine strains: an A/California/7/2009 (H1N1)pdm09-like virus; an A/Victoria/361/2011 (H3N2)-like virus; - a B/Wisconsin/1/2010-like virus.

Outcomes

Primary Outcome Measures

Immunogenicity of Trivalent Influenza Vaccine (TIV)by measuring Hemagglutination Inhibition Assays (HAI)
Humoral immunity will be measured by hemagglutination inhibition (HAI) assay, which has been extensively used for this purpose. In healthy individuals, HAI titers ≥1:10 indicate presence of influenza-specific antibodies and ≥1:40 protection against infection and disease. 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 titers; and sero-conversion will be defined as HAI titers from <1:10 to ≥1:40 or ≥4-fold increase if pre-vaccination titers were ≥1:10.

Secondary Outcome Measures

impact of vaccination on T-cell activation and on T- and B-cell subpopulations
T-lymphocyte activation assays will be performed using state-of-the art polychromatic flow cytometry. The T- and B-cell phenotypes are assessed by flow cytometry using freshly thawed Peripheral Blood Mononuclear Cells (PBMC). Cells are stained using monoclonal antibodies against the comparator molecules.
Impact of Vaccination of Cell Mediated Immune (CMI) Responses
Interferon(IFN)Enzyme Linked Immuno Spot (ELISPOT) responses will be used to assess CMI responses to influenza vaccines.PBMCs will be separated and stimulated with influenza virus corresponding to the vaccine strains. Spots will be visualized with a ELISPOT plate reader. Results will be reported as Spot Forming Cells(SFC)/106 PBMCs.
Local and Systemic solicited reactions to TIV
Participants will remain in the clinic for at least 30 minutes after vaccination so that clinic personnel can observe participants for any potential adverse reactions.Report of vaccine-related local (redness, swelling, tenderness, itching,) and systemic (fever, malaise, myalgia, nausea, headache, rash) adverse events will be solicited at day 7 and day 28.
safety outcome measures of TIV
Safety and tolerability of the study vaccine will be monitored by means of Adverse Events (AEs) and toxicity reports presenting laboratory and clinical data.Toxicities will be classified by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events,

Full Information

First Posted
March 13, 2013
Last Updated
December 10, 2013
Sponsor
University of Witwatersrand, South Africa
Collaborators
Bill and Melinda Gates Foundation
search

1. Study Identification

Unique Protocol Identification Number
NCT01812980
Brief Title
Immunogenicity and Safety of Trivalent Influenza Vaccine in Non-pregnant HIV-infected Women
Official Title
Immunogenicity and Safety of Trivalent Influenza Vaccine in Non-pregnant HIV- Infected Women: An Open Label Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
December 2013
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
July 2013 (Actual)
Study Completion Date
July 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Witwatersrand, South Africa
Collaborators
Bill and Melinda Gates Foundation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The overall aim of this project is to evaluate the immunogenicity of TIV vaccination in HIV-infected non-pregnant women in 2013. Safety data including solicited local and systemic reactions to the vaccine will also be assessed.
Detailed Description
Schedule of Events Visit 1 (enrollment) Informed Consent Form (ICF) signed Inclusion/ exclusion/ Withdrawal criteria Medical history Targeted physical exam Blood draw TIV administered Diary card dispensed Local/ systematic reactions Visit 2: 1 month post enrolment (28-35 days) Inclusion/ exclusion/ Withdrawal criteria Medical history Targeted physical exam Blood draw Diary card collected Local/ systematic reactions reviewed

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza, Human Immunodeficiency Virus
Keywords
Influenza, Human Immunodeficiency Virus

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
105 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Trivalent Inactivated Influenza Vaccine
Arm Type
Experimental
Arm Description
Single dose, intramuscular injection from a pre-filled syringe WHO recommendation for influenza vaccines for 2013 for the Southern-hemisphere included the following vaccine strains: an A/California/7/2009 (H1N1)pdm09-like virus; an A/Victoria/361/2011 (H3N2)-like virus; - a B/Wisconsin/1/2010-like virus.
Intervention Type
Biological
Intervention Name(s)
Trivalent Inactivated Influenza Vaccine
Other Intervention Name(s)
Vaxigrip
Intervention Description
WHO recommendation for influenza vaccines for 2013 for the Southern-hemisphere included the following vaccine strains: an A/California/7/2009 (H1N1)pdm09-like virus; an A/Victoria/361/2011 (H3N2)-like virus; - a B/Wisconsin/1/2010-like virus.
Primary Outcome Measure Information:
Title
Immunogenicity of Trivalent Influenza Vaccine (TIV)by measuring Hemagglutination Inhibition Assays (HAI)
Description
Humoral immunity will be measured by hemagglutination inhibition (HAI) assay, which has been extensively used for this purpose. In healthy individuals, HAI titers ≥1:10 indicate presence of influenza-specific antibodies and ≥1:40 protection against infection and disease. 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 titers; and sero-conversion will be defined as HAI titers from <1:10 to ≥1:40 or ≥4-fold increase if pre-vaccination titers were ≥1:10.
Time Frame
one month post vaccination
Secondary Outcome Measure Information:
Title
impact of vaccination on T-cell activation and on T- and B-cell subpopulations
Description
T-lymphocyte activation assays will be performed using state-of-the art polychromatic flow cytometry. The T- and B-cell phenotypes are assessed by flow cytometry using freshly thawed Peripheral Blood Mononuclear Cells (PBMC). Cells are stained using monoclonal antibodies against the comparator molecules.
Time Frame
one month post vaccination
Title
Impact of Vaccination of Cell Mediated Immune (CMI) Responses
Description
Interferon(IFN)Enzyme Linked Immuno Spot (ELISPOT) responses will be used to assess CMI responses to influenza vaccines.PBMCs will be separated and stimulated with influenza virus corresponding to the vaccine strains. Spots will be visualized with a ELISPOT plate reader. Results will be reported as Spot Forming Cells(SFC)/106 PBMCs.
Time Frame
one month post vaccination
Title
Local and Systemic solicited reactions to TIV
Description
Participants will remain in the clinic for at least 30 minutes after vaccination so that clinic personnel can observe participants for any potential adverse reactions.Report of vaccine-related local (redness, swelling, tenderness, itching,) and systemic (fever, malaise, myalgia, nausea, headache, rash) adverse events will be solicited at day 7 and day 28.
Time Frame
1 week and one month post vaccination
Title
safety outcome measures of TIV
Description
Safety and tolerability of the study vaccine will be monitored by means of Adverse Events (AEs) and toxicity reports presenting laboratory and clinical data.Toxicities will be classified by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events,
Time Frame
within one month post vaccination

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: (i) Documented to be HIV-1 infected on one assay used in the Prevention of Mother to Child Transmission (PMTCT)/ other program undertaken within 12 weeks of study enrolment. Able to understand and comply with planned study procedures. Provides written informed consent prior to initiation of study. Not pregnant at time of enrolment (confirmed by urine testing). If pregnant in past year, participant must be at least 6 months post delivery at time of enrolment. Women age ≥ 18 years to < 39 years. Exclusion Criteria: Receipt of TIV, other than through the study, during the current and previous two influenza seasons, documented by medical history or record. Receipt of any live licensed vaccine ≤ 28 days or any other vaccine (except for tetanus toxoid vaccine) ≤ 14 days prior to study-vaccine. Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or medication) ≤ 28 days prior to vaccination in this study, unless study approval is obtained. Any significant (in the opinion of the site investigator) acute illness and/or oral temperature greater than or equal to 38 degrees C ≤ 24 hours prior to study entry. Use of anti-cancer systemic chemotherapy or radiation therapy ≤ 48 weeks of study enrollment, or has immunosuppression as a result of an underlying illness or treatment. Long term use of glucocorticoids, including oral or parenteral prednisone ≥ 20 mg/day or equivalent for more than 2 consecutive weeks (or 2 weeks total) ≤ 12 weeks of study entry, or high-dose inhaled steroids (>800 mcg/day of beclomethasone dipropionate or equivalent) ≤ 12 weeks before study entry (nasal and topical steroids are allowed). Receipt of immunoglobulin or other blood products (with exception of Rho D immune globulin) ≤ 12 weeks prior to enrollment in this study or is scheduled to receive immunoglobulin or other blood products. Receipt of Interleukin 2, IFN, GMCSF or other immune mediators ≤ 12 weeks before enrollment. Uncontrolled major psychiatric disorder. History of a severe adverse reaction to previous TIV. Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.
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
Nrf/Dst Vpd Rmpru
City
Soweto
State/Province
Gauteng
Country
South Africa

12. IPD Sharing Statement

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Immunogenicity and Safety of Trivalent Influenza Vaccine in Non-pregnant HIV-infected Women

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