A Phase 2/3 interventional study of Trivalent influenza vaccine and Normal saline in Influenza, sponsored by University of Witwatersrand, South Africa. Completed at 1 site in South Africa. Open to female participants aged 18 Years to 39 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2013-02-07.
Sponsored by University of Witwatersrand, South Africa · Phase 2/3, Interventional, and Prevention
This randomized, placebo controlled trial will evaluate the safety and immunogenicity of Trivalent Influenza Vaccine (TIV) in HIV-infected pregnant women, dynamics of transplacental anti-influenza antibody transfer to their newborns and kinetics thereof during early infancy.
Determining the contribution of influenza to early childhood morbidity and mortality in sub-Saharan Africa and the potential to prevent influenza disease through vaccination may contribute to reducing childhood deaths; since influenza illness is a vaccine preventable disease for which vaccines are developed, licensed and available at reasonable cost. Unfortunately, infants at highest risk for serious disease are those under 6 months of age, for whom trivalent inactivated influenza vaccine (TIV) is poorly immunogenic and not licensed. As pregnant women also have an increased risk of serious illness (3.3-5.5 fold for hospitalization for influenza-associated acute cardio-respiratory illness) from influenza infection, one strategy to prevent the complications of influenza in pregnant women and young infants is through maternal TIV immunization, which is recommended by the WHO. This could result in direct protection of the women and protection of the young infant consequent to transplacental transfer of TIV induced antibody.
Barriers to administration of vaccines during pregnancy including lack of information on effectiveness and concerns about safety probably explain the virtual non-existent use of TIV in pregnant women from low-middle income countries, including South Africa.
The immunogenicity and efficacy of TIV in HIV-infected adults was only recently documented in an African setting. A placebo-controlled, community-based randomized, placebo controlled trial, conducted in South Africa reported that TIV was associated with a 75% reduction in influenza-confirmed illness. The results of the study also confirmed the safety of TIV among African HIV-infected adults. The study, however, only included 7 women who were pregnant. In addition to no differences in solicited adverse event rates, there was also no difference in either CD4+ cell count changes or HIV viral control in those on antiretroviral treatment between TIV vaccinees compared to placebo recipients. This allayed previous concerns regarding the potential negative effect of TIV which centered around the observed transient increase in HIV-1 viral load, even in HIV infected individuals on ART and who were virologically suppressed (viral load \<400 copies/ml). Decreases in CD4+ lymphocyte counts have also been observed in HIV-infected individuals post TIV vaccination. These changes, however, even in past studies were infrequent (4-18%) and resolved at later time-points and were considered to be clinically non-significant.
Only recently has data become available from Bangladesh in which the benefit of maternal TIV vaccination was demonstrated by a 63% (95%CI 5 to 85) reduction in laboratory-confirmed influenza illness in infants under 24 weeks of age in children born to mothers vaccinated with TIV and a 36% reduction in clinical illness in vaccinated mothers. There has, however, not been any study on the effectiveness of maternal immunization with TIV on influenza- associated morbidity and mortality either in the mothers or infants in African settings.
Despite the encouraging results on maternal immunization from Bangladesh, and the preliminary data supporting that TIV is efficacious mainly in HIV-infected non-pregnant adults, further data are needed to advocate for routine use of TIV during pregnancy in settings with a high prevalence of HIV. Reasons for this include that the impact of maternal HIV on the kinetics of TIV induced transplacental antibody transfer cannot be derived from available data. This is important as the primary focus of this proposal, and major potential public health benefit of maternal TIV vaccination, is targeted at protection of young infants. HIV infection is known to decrease placental integrity and lower antibody levels in the fetus and newborn. Furthermore, maternal hypergamma-globulinemia that is characteristic of HIV-infection may be associated with decreased neonatal antibody levels. This paradox is explained by the limited number of placental antibody receptors, resulting in IgG antibodies competing for available receptors and thereby decreasing vaccine-specific antibody transport. Preterm birth increases with HIV, chronic maternal disease or malnutrition. Transfer of maternal antibody which is gestational age dependant, may be more affected by maternal immunization in sub-Saharan Africa where these conditions are common.
The overall aim of this project is to evaluate the safety and immunogenicity of TIV vaccination of HIV-infected pregnant women
2,215 studies on the registry are indexed under Influenza, Human; 164 are open to participants now.
This study's enrollment of 194 is below the median of 239 across 1,854 interventional studies indexed under Influenza, Human.
Browse Influenza, Human studies →University of Witwatersrand, South Africa is the lead sponsor of 46 studies on the registry; 4 are open to participants now.
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Exclusion Criteria
0.5ml of TIV will be administered into deltoid muscle of non dominant arm
Biological: Trivalent influenza vaccine
0.5ml of normal saline administered into deltoid muscle of non dominant arm
Biological: Normal saline
0.5 ml of trivalent influenza vaccine administered into deltoid muscle of non dominant arm
Also known as: Vaxigrip
0.5ml normal saline administered into deltoid muscle of non dominant arm
Also known as: NaCl
Humoral immune responses to influenza strains in the vaccine will be measured to assess the immunogenicity of TIV in HIV-infected pregnant women vaccinated between 20-34 weeks of gestational age
Humoral immunity will be measured by hemagglutination inhibition (HAI) assay. Blood will be collected at enrolment (pre-vaccination), one month post vaccination, delivery (+7 days) and 24 weeks post delivery. Humoral immune response definitions: HAI titers \< 1:10 = seronegative; ≥ 1:10 = seropositive; \> 1:40 = protected against influenza; Response to TIV = serconversion (from \<1:10 to ≥1:10) and/or 4-fold increase of HAI titers.
Time frame: 1 month post vaccination, delivery (+7 days), 24 weeks post delivery
The proportion of newborns born to HIV-infected mothers with hemagglutination inhibition (HAI) antibody titers of ≥1:40 to TIV strain will be determined and compared to newborns born to TIV-vaccinated HIV-uninfected women (parallel trial)
Determine the proportion of newborns with hemagglutination inhibition (HAI) antibody titers of ≥1:40 to each of the three TIV strains born to HIV-infected mothers and compared to newborns born to TIV-vaccinated HIV-uninfected women
Time frame: Delivery (+7 days)
Hemagglutinin (HA) antibody measurements in blood taken from mother and infants up to 24 weeks post delivery will be used to assess dynamics and kinetics of transplacentally acquired antibodies
Hemagglutinin (HA) antibody measurements in blood taken from mother at birth and infants at birth, 8,16 and 24 weeks post delivery will be used to assess dynamics and kinetics of transplacentally acquired antibodies
Time frame: 24 weeks post partum
The number of laboratory-confirmed or clinical influenza like illness cases in infants born to HIV infected mothers who received TIV or placebo will be used to determine efficacy of TIV vaccination of pregnant women against ILI in their infants
All infants (up to 24 weeks of age) born to women enrolled on trial will be assessed by study staff if they have any signs or symptoms (including fever, hospitalisation, apnea, cough, nasal catarrh/ congenstion, tachypnea) which could indicate influenza like illness. Nasopharyngeal aspirate samples collected at illness visits will be processed for viruses using real time reverse transcriptase-polymerase chain reaction (rRTPCR) assays.
Time frame: 24 weeks of age
The number of laboratory-confirmed influenza illnesses and clinical ILI cases in maternal participants during pregnancy and for 24 weeks post-partum will be used to assess efficacy of TIV against laboratory confirmed and clinical ILI
All maternal participants with signs and/ or symptoms of influenza like illness (ILI) will have nasopharyngeal and oropharyngeal swabs collected at illness visits and processed by rRTPCR assays. Participants from whom influenza virus is isolated at illness visits will be included in analysis to evaluate the efficacy of TIV against laboratory-confirmed influenza illness in mothers during pregnancy and until 24 weeks post-partum. Participants with no influenza isolated will be included in analysis of clinical ILI.
Time frame: 24 weeks
Cell-mediated immune (CMI) responses to influenza strains in the vaccine will be measured to define CMI responses to TIV in HIV infected pregnant women
Cell mediated immunity will be measured by ELISPOT response to TIV. Blood will be collected at enrollment (pre-vaccination) and one month post vaccination
Time frame: 1 month post vaccination
CD4+ and HIV-viral load will be measured at baseline and one-month post vaccination to evaluate effect of TIV.
Evaluate the effect of TIV on CD4+ and HIV-viral load changes comparing baseline levels to one-month post vaccination.
Time frame: 1 month post vaccination
This study is completed, as verified in Feb 2013. You cannot join it, but the record below documents what was studied.
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University of Witwatersrand, South Africa