Influenza
Conditions
Keywords
Influenza, Vaccination
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.
Interventions
BIOLOGICALTrivalent Influenza Vaccine
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.
Sponsors
Bill and Melinda Gates Foundation
University of Witwatersrand, South Africa
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 39 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Compare the immunogenicity of Trivalent Influenza Vaccine (TIV) in pregnant compared to non-pregnant Human Immunodeficiency Virus (HIV)-uninfected women. | one month post-vaccination | 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 | one week post delivery for the pregnant cohort | 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
| Measure | Time frame | Description |
|---|---|---|
| Determine the dynamics of transplacental transfer of maternal Hemagglutinin (HA) antibodies to their newborns. | one week post delivery in pregnant cohort | 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 | in week post delivery | Influenza specific antibodies measures by HAI titres in the breastmilk will be measured. Mothers will express breastmilk into sterile containers to collect the samples. |
| Determine the impact of vaccination on T-cell activation and regulatory B and T cells subpopulations in pregnant and non-pregnant women. | one month post vaccination and one week post delivery in pregnant cohort | 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 |
| Describe safety outcome measures (maternal and foetal) of TIV-vaccination of HIV-uninfected pregnant women. | one month post vaccination and one week post delivery in pregnant cohort | 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 | one week post delivery in pregnant cohort | Data will be collected from birth records including low birth weight (\<2 500 g), premature delivery (\<37 weeks), emergency caesarean section |
| Compare local and systemic solicited reactions to TIV in pregnant and non-pregnant HIV-uninfected women. | one month post vaccination | 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. |
| 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 | one month post vaccination | 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. |
Countries
South Africa
Outcome results
None listed