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Prevention of vaccine-matched and mismatched influenza in children aged 6–35 months: a multinational randomised trial across five influenza seasons

2018; Elsevier BV; Volume: 2; Issue: 5 Linguagem: Inglês

10.1016/s2352-4642(18)30062-2

2352-4650

Carine Claeys, Khalequ Zaman, Ghassan Dbaibo, Ping Li, Allen Izu, Pope Kosalaraksa, Luis Rivera, Beatriz Acosta, Maria Basanta, Asma Binte Aziz, Miguel Angel Cabanero, Vijayalakshmi Chandrashekaran, Bartholomew Corsaro, Luis Cousin, Adolfo Diaz, Javier Díez‐Domingo, Ener Çağrı Dinleyici, Saul N. Faust, Damien Friel, José García-Sicilia, Grace Devota Gomez-Go, Maria Gonzales, Stephen Hughes, Teresa Jackowska, Shashi Kant, Marilla Lucero, Ludovic Malvaux, Josep Marès Bermúdez, Federico Martinón‐Torres, Mariano Miranda, May Montellano, Maria Amor Peix Sambola, Roman Prymula, Thanyawee Puthanakit, Renáta Růžková, Iwona Sadowska-Krawczenko, Ignacio Salamanca de la Cueva, Étienne Sokal, Jyoti Soni, Henryk Szymański, Àngels Ulied, Anne Schuind, Varsha Jain, Bruce L. Innis, Beatriz Acostas, Arshad Amanullah, Miguel Ariza, Maria Basanta, Asma Binte Aziz, Milagros Bautista, Ashish Bavdekar, Bhavesh Bodalia, Lulu Bravo, Jerzy Brzostek, Miguel Angel Cabanero, I Caldwell, Alfonso Carmona, Vijayalakshmi Chandrashekaran, Carine Claeys, Bartholomew Corsaro, Luis Cousin, Jasur Danier, Ghassan Dbaibo, Ana Isabel Diaz Cirujano, Adolfo Diaz, Javier Díez‐Domingo, Ener Çağrı Dinleyici, M. Docx, Daniel Dražan, Saul N. Faust, Andrzej Gałaj, Fermin Garcia Rodriguez, José García-Sicilia, Maria Gonzales, Grace Devota Gomez-Go, Trevor Gooding, Mustafa Hacımustafaoğlu, Paul T. Heath, Paul Heaton, Stephen Hughes, Bruce L. Innis, Allen Izu, Teresa Jackowska, Varsha Jain, Shashi Kant, Pope Kosalaraksa, Sanjay Lalwani, Jennifer Langlands, Ping Li, Karl Logghe, Marilla Lucero, Ludovic Malvaux, J. Mantyka, Josep Marès Bermúdez, Federico Martinón‐Torres, Damien McNally, Edyta Miszczak-Kowalska, May Montellano, Maria Amor Peix Sambola, Roman Prymula, Thanyawee Puthanakit, Luis Rivera, Simon Royal, Renáta Růžková, Benjamin Sablan, Iwona Sadowska-Krawczenko, Ignacio Salamanca de la Cueva, Anne Schuind, Matthew D. Snape, Jyoti Soni, Richard Tomlinson, Àngels Ulied, Marc Verghote, André Vertruyen, M M Wheeler, Khalequ Zaman,

Pneumonia and Respiratory Infections

Despite 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.In 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.Between 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.IIV4 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.GlaxoSmithKline Biologicals SA.