Randomized, placebo-controlled trial on safety and efficacy of inactivated influenza vaccination of pregnant women in preventing illness in their infants

Abstract

Background: Pregnant women and young infants are at increased risk for severe influenza-illness. Influenza vaccination during pregnancy may confer indirect protection against influenzaillness to infants < 6 months of age, for whom there is no licensed influenza vaccine. A co-primary objective of our study was to evaluate the efficacy of trivalent inactivated influenza vaccine (IIV3) when given during pregnancy against PCR-confirmed influenzaillness (PCI) in their infants up until 6 months of age. Methods & Materials: We conducted a double-blind, randomized, placebo-controlled trial in Soweto, South Africa during the 2011 and 2012 influenza seasons. 2116 HIV-uninfected women were randomized to receive IIV3 or placebo intramuscularly between 20-36 weeks gestation. Infants were screened weekly for influenza-like-illness (ILI) after birth. When ILI was suspected nasopharyngeal aspirates were collected for influenza A and B testing by real-time PCR. Influenza A viruses were subtyped for A/H1N1pdm09 and H3N2 and influenza B isolates were tested for Yamagata and Victoria lineages. Results: Pregnancy outcomes were similar between the IIV3 and placebo-group, including 8 miscarriages and 22 stillbirths. 2048 babies were born alive, 1025 and 1023 to mothers who received IIV3 and placebo, respectively. The rates of preterm deliveries (10%) and low birth weight (12.4%) were also similar between the study groups. 706 and 698 illness visits were completed in infants of mothers who received IIV3 and placebo, respectively; of which 665 (64.9%) and 656 (64.1%) illness episodes fulfilled ILI criteria. In infants born to IIV3-recipients, 19 PCI cases were detected compared to 37 in infants born to placebo-recipients, resulting in vaccine efficacy of 48.8% (95%CI: 11.5% to 70.3%) against PCI in infants. Excluding the non-vaccine influenza B/Yamagata cases from the analysis vaccine efficacy (VE) did not change (VE: 48.1%; 95%CI: -0.9% to 73.3%). In twelve (21.4%) of the 56 PCI cases among infants (including 11 whose mothers received placebo), PCI was also identified concurrently in the mother. Conclusion: Vaccination of African pregnant women with IIV3 was safe and reduced PCI in their infants by 49% up until 6 months of age. Immunization of pregnant women with IIV3 is warranted for the protection of their young infants.