Back to resultsImmunogenicity and Safety of Trivalent Influenza Vaccine in Pregnant and Nonpregnant HIV Uninfected Women
Primary Purpose
Influenza
Status
Completed
Phase
Phase 4
Locations
South Africa
Study Type
Interventional
Intervention
Trivalent Influenza Vaccine
Sponsored by
About this trial
This is an interventional basic science trial for Influenza focused on measuring Influenza, Vaccination
Eligibility Criteria
Inclusion Criteria:
Inclusion Criteria: All women
(i) Documented to be HIV-1 uninfected on one assay used in the Prevention of Mother to Child Transmission (PMTCT)/ other program undertaken within 12 weeks of study enrolment.
(ii) Able to understand and comply with planned study procedures. (iii) Provides written informed consent prior to initiation of study. (iv) Women age ≥ 18 years to < 39 years.
Inclusion Criteria: pregnant women
(i) Gestational age ≥20 weeks to <36 weeks documented by the approximate date of the last menstrual period and corroborated by physical exam and sonar report if available.
Exclusion Criteria:
Exclusion Criteria: All women
(i) Receipt of TIV, other than through the study, during the current influenza season documented by medical history or record.
(ii) Receipt of any live licensed vaccine ≤ 28 days or any other vaccine (except for tetanus toxoid vaccine) ≤ 14 days prior to study-vaccine.
(iii) Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or medication) ≤ 28 days prior to vaccination in this study, or expects to receive another non-licensed agent before delivery unless study approval is obtained.
(iv) 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.
(v) 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.
(vi) 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).
(vii) 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 (with the exception of Rho D immune globulin) during pregnancy or for the first 24 weeks after delivery.
(viii) Receipt of immune mediators ≤ 12 weeks before enrollment. (ix) Uncontrolled major psychiatric disorder. (x) History of a severe adverse reaction to previous TIV. (xi) 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.
Exclusion Criteria: pregnant women
(i) Receipt of corticosteroids for preterm labor ≤ 14 days before study entry. (ii) Pregnancy complications (in the current pregnancy) such as pre-term labor, hypertension (Blood Pressure (BP) >140/90 in the presence of proteinuria or BP >150/100, with or without proteinuria or currently on antihypertensive medication) or pre-eclampsia.
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Sites / Locations
- Nrf/Dst Vpd Rmpru
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Trivalent Influenza Vaccine
Arm Description
The formulation based on the 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. Dose: Single Dose 0.5 mL of TIV from pre-filled syringe.
Outcomes
Primary Outcome Measures
Compare the immunogenicity of Trivalent Influenza Vaccine (TIV) in pregnant compared to non-pregnant Human Immunodeficiency Virus (HIV)-uninfected women.
Hemagglutination inhibition assays (HAI)will be performed to assess the immunogenicity of TIV. 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.
Evaluate the immunogenicity of Trivalent Influenza Vaccine (TIV) in pregnant Human Immunodeficiency Virus (HIV)-uninfected women at time of delivery
Hemagglutination inhibition assays (HAI)will be performed to assess the immunogenicity of TIV. 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
Determine the impact of vaccination on T-cell activation and regulatory B and T cells subpopulations in pregnant and non-pregnant women.
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
2.2.2. Determine the impact of vaccination on cell-mediated immune responses to each influenza strain in HIV-uninfected pregnant and non-pregnant women
Interferon (IFN)- Enzyme Linked Immuno Spot (ELISPOT) responses will be assessed on fresh PBMCs. 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.
Determine the dynamics of transplacental transfer of maternal Hemagglutinin (HA) antibodies to their newborns.
The study will assess the effect of TIV administration during pregnancy on transplacental influenza-specific antibody transfer to the fetus. HAI titers will be measured in infants within one week of birth. Using the 1:40 HAI titer as a defining threshold of protection against wild type influenza, we will determine the proportion of infants protected against influenza at birth.
Determine antibodies against TIV present in breast milk
Influenza specific antibodies measures by HAI titres in the breastmilk will be measured. Mothers will express breastmilk into sterile containers to collect the samples.
Compare local and systemic solicited reactions to TIV in pregnant and non-pregnant HIV-uninfected women.
Participants will remain in the clinic for at least 30 minutes after vaccination so that clinic personnel can observe for any potential adverse reactions to the vaccine.
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 by means of a participant diary card. Serious Adverse Events (SAEs) will be reported.
Describe safety outcome measures (maternal and foetal) of TIV-vaccination of HIV-uninfected pregnant women.
Safety and tolerability of the study vaccine will be monitored by means of Adverse Events (AEs) and toxicity reports presenting laboratory and clinical data. The data to be reviewed by the protocol team will be pooled across treatment arms.In addition to monthly toxicity reviews by the Core Team, the study will be monitored by a Safety Monitoring Committee (SMC). The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events is used
Describe obstetric outcomes in HIV-uninfected pregnant women who received TIV
Data will be collected from birth records including low birth weight (<2 500 g), premature delivery (<37 weeks), emergency caesarean section
Full Information
NCT ID
NCT01816464
First Posted
March 14, 2013
Last Updated
January 9, 2015
Sponsor
University of Witwatersrand, South Africa
Collaborators
Bill and Melinda Gates Foundation
1. Study Identification
Unique Protocol Identification Number
NCT01816464
Brief Title
Immunogenicity and Safety of Trivalent Influenza Vaccine in Pregnant and Nonpregnant HIV Uninfected Women
Official Title
Immunogenicity and Safety of Trivalent Influenza Vaccine in Pregnant and Non-pregnant HIV-Uninfected Women: An Open Label Trial
Study Type
Interventional
2. Study Status
Record Verification Date
January 2015
Overall Recruitment Status
Completed
Study Start Date
September 2013 (undefined)
Primary Completion Date
February 2014 (Actual)
Study Completion Date
April 2014 (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-uninfected pregnant women compared with HIV-uninfected non-pregnant women in 2013. Safety data will also be collected.THe Pregnancy outcomes and the transplacental transfer of antibodies will also be assessed.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Influenza
Keywords
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
150 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Trivalent Influenza Vaccine
Arm Type
Experimental
Arm Description
The formulation based on the 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.
Dose: Single Dose 0.5 mL of TIV from pre-filled syringe.
Intervention Type
Biological
Intervention Name(s)
Trivalent Influenza Vaccine
Other Intervention Name(s)
Vaxigrip
Intervention Description
The formulation based on the 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.
The vaccine to be used in the study in 2013 is Vaxigrip (Sanofi Pasteur), or other equivalent licensed vaccine should the latter not be available, which will be procured commercially in pre-filled syringes. Using aseptic technique, participants will be injected with 0.5 mL of TIV from pre-filled syringe.
Primary Outcome Measure Information:
Title
Compare the immunogenicity of Trivalent Influenza Vaccine (TIV) in pregnant compared to non-pregnant Human Immunodeficiency Virus (HIV)-uninfected women.
Description
Hemagglutination inhibition assays (HAI)will be performed to assess the immunogenicity of TIV. 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
Title
Evaluate the immunogenicity of Trivalent Influenza Vaccine (TIV) in pregnant Human Immunodeficiency Virus (HIV)-uninfected women at time of delivery
Description
Hemagglutination inhibition assays (HAI)will be performed to assess the immunogenicity of TIV. 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 week post delivery for the pregnant cohort
Secondary Outcome Measure Information:
Title
Determine the impact of vaccination on T-cell activation and regulatory B and T cells subpopulations in pregnant and non-pregnant women.
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 and one week post delivery in pregnant cohort
Title
2.2.2. Determine the impact of vaccination on cell-mediated immune responses to each influenza strain in HIV-uninfected pregnant and non-pregnant women
Description
Interferon (IFN)- Enzyme Linked Immuno Spot (ELISPOT) responses will be assessed on fresh PBMCs. 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
Determine the dynamics of transplacental transfer of maternal Hemagglutinin (HA) antibodies to their newborns.
Description
The study will assess the effect of TIV administration during pregnancy on transplacental influenza-specific antibody transfer to the fetus. HAI titers will be measured in infants within one week of birth. Using the 1:40 HAI titer as a defining threshold of protection against wild type influenza, we will determine the proportion of infants protected against influenza at birth.
Time Frame
one week post delivery in pregnant cohort
Title
Determine antibodies against TIV present in breast milk
Description
Influenza specific antibodies measures by HAI titres in the breastmilk will be measured. Mothers will express breastmilk into sterile containers to collect the samples.
Time Frame
in week post delivery
Title
Compare local and systemic solicited reactions to TIV in pregnant and non-pregnant HIV-uninfected women.
Description
Participants will remain in the clinic for at least 30 minutes after vaccination so that clinic personnel can observe for any potential adverse reactions to the vaccine.
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 by means of a participant diary card. Serious Adverse Events (SAEs) will be reported.
Time Frame
one month post vaccination
Title
Describe safety outcome measures (maternal and foetal) of TIV-vaccination of HIV-uninfected pregnant women.
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. The data to be reviewed by the protocol team will be pooled across treatment arms.In addition to monthly toxicity reviews by the Core Team, the study will be monitored by a Safety Monitoring Committee (SMC). The Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events is used
Time Frame
one month post vaccination and one week post delivery in pregnant cohort
Title
Describe obstetric outcomes in HIV-uninfected pregnant women who received TIV
Description
Data will be collected from birth records including low birth weight (<2 500 g), premature delivery (<37 weeks), emergency caesarean section
Time Frame
one week post delivery in pregnant cohort
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:
Inclusion Criteria: All women
(i) Documented to be HIV-1 uninfected on one assay used in the Prevention of Mother to Child Transmission (PMTCT)/ other program undertaken within 12 weeks of study enrolment.
(ii) Able to understand and comply with planned study procedures. (iii) Provides written informed consent prior to initiation of study. (iv) Women age ≥ 18 years to < 39 years.
Inclusion Criteria: pregnant women
(i) Gestational age ≥20 weeks to <36 weeks documented by the approximate date of the last menstrual period and corroborated by physical exam and sonar report if available.
Exclusion Criteria:
Exclusion Criteria: All women
(i) Receipt of TIV, other than through the study, during the current influenza season documented by medical history or record.
(ii) Receipt of any live licensed vaccine ≤ 28 days or any other vaccine (except for tetanus toxoid vaccine) ≤ 14 days prior to study-vaccine.
(iii) Receipt of a non-licensed agent (vaccine, drug, biologic, device, blood product, or medication) ≤ 28 days prior to vaccination in this study, or expects to receive another non-licensed agent before delivery unless study approval is obtained.
(iv) 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.
(v) 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.
(vi) 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).
(vii) 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 (with the exception of Rho D immune globulin) during pregnancy or for the first 24 weeks after delivery.
(viii) Receipt of immune mediators ≤ 12 weeks before enrollment. (ix) Uncontrolled major psychiatric disorder. (x) History of a severe adverse reaction to previous TIV. (xi) 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.
Exclusion Criteria: pregnant women
(i) Receipt of corticosteroids for preterm labor ≤ 14 days before study entry. (ii) Pregnancy complications (in the current pregnancy) such as pre-term labor, hypertension (Blood Pressure (BP) >140/90 in the presence of proteinuria or BP >150/100, with or without proteinuria or currently on antihypertensive medication) or pre-eclampsia.
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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
GP
ZIP/Postal Code
2055
Country
South Africa
12. IPD Sharing Statement
Learn more about this trial
Immunogenicity and Safety of Trivalent Influenza Vaccine in Pregnant and Nonpregnant HIV Uninfected Women
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