GlaxoSmithKline Biologicals SA.

Background: We evaluated an inactivated quadrivalent influenza vaccine (IIV4) in children 6–35 months of age in a phase III, observer-blind trial. Methods: The aim of this analysis was to estimate vaccine efficacy (VE) in preventing laboratory-confirmed influenza in each of 5 independent seasonal cohorts (2011−2014), as well as vaccine impact on healthcare utilization in 3 study regions (Europe/Mediterranean, Asia-Pacific and Central America). Healthy children were randomized 1:1 to IIV4 or control vaccines. VE was estimated against influenza confirmed by reverse transcription polymerase chain reaction on nasal swabs. Cultured isolates were characterized as antigenically matched/mismatched to vaccine strains. Results: The total vaccinated cohort included 12,018 children (N = 1777, 2526, 1564, 1501 and 4650 in cohorts 1−5, respectively). For reverse transcription polymerase chain reaction confirmed influenza of any severity (all strains combined), VE in cohorts 1−5 was 57.8%, 52.9%, 73.4%, 30.3% and 41.4%, respectively, with the lower limit of the 95% confidence interval >0 for all estimates. The proportion of vaccine match for all strains combined in each cohort was 0.9%, 79.3%, 72.5%, 24.1% and 28.6%, respectively. Antibiotic use associated with influenza illness was reduced with IIV4 by 71% in Europe, 36% in Asia Pacific and 59% in Central America. Conclusions: IIV4 prevented influenza in children 6−35 months of age in each of 5 separate influenza seasons in diverse geographical regions. A possible interaction between VE, degree of vaccine match and socioeconomic status was observed. The IIV4 attenuated the severity of breakthrough influenza illness and reduced healthcare utilization, particularly antibiotic use.

Background A new inactivated polio vaccine made from Sabin strains (sIPV) was developed as part of the global polio eradication initiative. Methods This randomized, double-blind, active-controlled, phase 2/3 seamless study was conducted in 2 stages. Healthy infants aged 6 weeks were randomly assigned to receive 3 doses of 1 of 4 study vaccines at 6, 10, and 14 weeks of age (336 received low-, middle-, or high-dose sIPV, or conventional IPV [cIPV] in stage I, and 1086 received lot A, B, or C of the selected sIPV dose, or cIPV in stage II). The primary outcome was the seroconversion rate 4 weeks after the third vaccination. Results In stage I, low-dose sIPV was selected as the optimal dose. In stage II, consistency among the 3 manufacturing lots of sIPV was demonstrated. The seroconversion rates for Sabin and wild strains of the 3 serotypes after the 3-dose primary series were 95.8% to 99.2% in the lot-combined sIPV group and 94.8% to 100% in the cIPV group, proving the noninferiority of sIPV compared to cIPV. No notable safety risks associated with sIPV were observed. Conclusions Low-dose sIPV administered as a 3-dose vaccination was safe and immunogenic compared to cIPV. Clinical Trials Registration NCT03169725.

Background: In an exploratory analysis of an inactivated quadrivalent influenza vaccine (IIV4) trial in children 6–35 months without risk factors for influenza, we evaluated clinical presentation of influenza illness and vaccine impact on health outcomes. Methods: This phase III trial was conducted in 13 geographically diverse countries across 5 influenza seasons (2011–2014). Children were randomized 1:1 to IIV4 or control. Active surveillance was performed for influenza-like episodes (ILE); influenza was confirmed by reverse transcription polymerase chain reaction (RT-PCR). The total vaccinated cohort was evaluated (N = 12,018). Results: 5702 children experienced ≥1 ILE; 356 (IIV4 group) and 693 (control group) children had RT-PCR-confirmed influenza. Prevalence of ILE was similar in RT-PCR-positive and RT-PCR-negative cases regardless of vaccination. Breakthrough influenza illness was attenuated in children vaccinated with IIV4; moderate-to-severe illness was 41% less likely to be reported in the IIV4 group than the control group [crude odds ratio: 0.59 (95% confidence intervals: 0.44−0.77)]. Furthermore, fever >39°C was 46% less frequent following vaccination with IIV4 than with control [crude odds ratio: 0.54 (95% confidence intervals: 0.39−0.75)] in children with breakthrough illness. Health outcome analysis showed that, each year, IIV4 would prevent 54 influenza cases per 1000 children and 19 children would need to be vaccinated to prevent 1 new influenza case. Conclusions: In addition to preventing influenza in 50% of participants, IIV4 attenuated illness severity and disease burden in children who had a breakthrough influenza episode despite vaccination.