1. Prevention of vaccine-matched and mismatched influenza in children aged 6-35 months: a multinational randomised trial across five influenza seasons
- Author
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Carine Claeys, Khalequ Zaman, Ghassan Dbaibo, Ping Li, Allen Izu, Pope Kosalaraksa, Luis Rivera, Beatriz Acosta, Maria Luisa Arroba Basanta, Asma Aziz, Miguel Angel Cabanero, Vijayalakshmi Chandrashekaran, Bartholomew Corsaro, Luis Cousin, Adolfo Diaz, Javier Diez-Domingo, Ener Cagri Dinleyici, Saul N Faust, Damien Friel, Jose Garcia-Sicilia, Grace D Gomez-Go, Maria Liza Antoinette Gonzales, Stephen M Hughes, Teresa Jackowska, Shashi Kant, Marilla Lucero, Ludovic Malvaux, Josep Mares Bermudez, Federico Martinon-Torres, Mariano Miranda, May Montellano, Maria Amor Peix Sambola, Roman Prymula, Thanyawee Puthanakit, Renata Ruzkova, Iwona Sadowska-Krawczenko, Ignacio Salamanca de la Cueva, Etienne Sokal, Jyoti Soni, Henryk Szymanski, Angels Ulied, Anne Schuind, Varsha K Jain, Bruce L Innis, Beatriz Acostas, Arshad Amanullah, Miguel Ariza, Milagros Bautista, Ashish Bavdekar, Bhavesh Bodalia, Lulu C Bravo, Jerzy Brzostek, Ian Caldwell, Alfonso Carmona, Jasur Danier, Ana Isabel Diaz Cirujano, Martine Docx, Daniel Drazan, Andrzej Galaj, Fermin Garcia Rodriguez, Trevor Gooding, Mustafa Hacimustafaoglu, Paul Heath, Paul Heaton, Sanjay Lalwani, Jennifer Langlands, Karl Logghe, Jolanta Mantyka, Damien McNally, Edyta Miszczak-Kowalska, Simon Royal, Benjamin Sablan, Matthew Snape, Richard Tomlinson, Marc Verghote, Andre Vertruyen, and Marie Wheeler
- Subjects
Male ,medicine.medical_specialty ,Internationality ,Disease ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Vaccine strain ,Disease severity ,Randomized controlled trial ,law ,030225 pediatrics ,Internal medicine ,Influenza, Human ,Developmental and Educational Psychology ,medicine ,Humans ,Single-Blind Method ,030212 general & internal medicine ,business.industry ,Infant ,Vaccine efficacy ,Clinical trial ,Vaccine mismatch ,Influenza Vaccines ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Cohort ,Female ,Seasons ,business - Abstract
BackgroundDespite the importance of vaccinating children younger than 5 years, few studies evaluating vaccine prevention of influenza have been reported in this age group. We evaluated efficacy of an inactivated quadrivalent influenza vaccine (IIV4) in children aged 6–35 months.MethodsIn this phase 3, observer-blinded, multinational trial, healthy children from 13 countries in Europe, Central America, and Asia were recruited in five independent cohorts, each in a different influenza season. Participants were randomly assigned (1:1) to either IIV4 (15 μg haemagglutinin antigen per strain per 0·5 mL dose; a single dose on day 0 for vaccine-primed children, and two doses, on days 0 and 28, for vaccine-unprimed children) or to one or two doses of a non-influenza control vaccine. Primary endpoints were moderate-to-severe influenza or all influenza (irrespective of disease severity) confirmed by RT-PCR on nasal swabs. Cultured isolates were further characterised as antigenically matched or mismatched to vaccine strains. Efficacy was assessed in the per-protocol cohort and total vaccinated cohort (time-to-event analysis), and safety was assessed in the total vaccinated cohort.FindingsBetween Oct 1, 2011, and Dec 31, 2014, 12 018 children were recruited into the total vaccinated cohort (6006 children in the IIV4 group and 6012 children in the control group). 356 (6%) children in the IIV4 group and 693 (12%) children in the control group had at least one case of RT-PCR-confirmed influenza. Of these 1049 influenza strains, 138 (13%) were A/H1N1, 529 (50%) were A/H3N2, 69 (7%) were B/Victoria, and 316 (30%) were B/Yamagata. Overall, 539 (64%) of 848 antigenically characterised isolates were vaccine-mismatched (16 [15%] of 105 for A/H1N1; 368 [97%] of 378 for A/H3N2; 54 [86%] of 63 for B/Victoria; 101 [33%] of 302 for B/Yamagata). Vaccine efficacy was 63% (97·5% CI 52–72) against moderate-to-severe influenza and 50% (42–57) against all influenza in the per-protocol cohort, and 64% (53–73) against moderate-to-severe influenza and 50% (42–57) against all influenza in the total vaccinated cohort. There were no clinically meaningful safety differences between IIV4 and control.InterpretationIIV4 prevented influenza A and B in children aged 6–35 months despite high levels of vaccine mismatch. Vaccine efficacy was highest against moderate-to-severe disease, which is the most clinically important endpoint associated with greatest burden.FundingGlaxoSmithKline Biologicals SA.
- Published
- 2017