Influenza Vaccination of HIV Infected Pregnant Women: Safety and Immunogenicity
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      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.
    

Detailed description: 
      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
    

Intervention name(s): Trivalent influenza vaccine; Normal saline
Intervention type(s): Biological; Biological
Intervention description(s): 0.5 ml of trivalent influenza vaccine administered into deltoid muscle of non dominant arm; 0.5ml normal saline administered into deltoid muscle of non dominant arm
Other intervention name(s): Vaxigrip; NaCl
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention