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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

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

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.

Methods

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.

Findings

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.

Interpretation

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.

Funding

GlaxoSmithKline Biologicals SA.
338-349
Claeys, C.
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Zaman, K.
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Dbaibo, G.
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Li, P.
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Izu, A.
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Kosalaraksa, P
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Rivera, L.
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Acosta, B.
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Arroba Basanta, M.L.
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Aziz, A.
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Corsaro, B.
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Hughes, S.M.
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Jackowska, T.
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Kant, S.
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Lucero, M.
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Malvaux, L.
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Mares Bermudez, J.
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Martinon-Torres, F.
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Miranda, M.
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Montellano, M.
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Ruzkova, R.
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Sadowska-Krawczenko, I.
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Salamanca de la Cueva, I.
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Sokal, E.
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Soni, J.
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Szymanski, H.
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Schuind, A.
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Innis, B.L.
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Claeys, C.
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Zaman, K.
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Dbaibo, G.
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Li, P.
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Izu, A.
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Kosalaraksa, P
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Rivera, L.
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Acosta, B.
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Arroba Basanta, M.L.
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Aziz, A.
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Cabanero, M.A.
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Chandrashekaran, V.
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Corsaro, B.
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Cousin, L.
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Diaz, A.
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Diez-Domingo, J.
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Dinleyici, E.C.
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Faust, S.N.
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Friel, D.
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Garcia-Sicilia, J.
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Go, G.D.
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Gonzales, M.L.A.
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Hughes, S.M.
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Kant, S.
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Lucero, M.
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Malvaux, L.
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Mares Bermudez, J.
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Martinon-Torres, F.
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Miranda, M.
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Montellano, M.
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Peix Sambola, M.A.
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Prymula, R.
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Sokal, E.
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Soni, J.
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Ulied, A.
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Schuind, A.
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Jain, V.K.
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Innis, B.L.
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Claeys, C., Zaman, K., Dbaibo, G., Li, P., Izu, A., Kosalaraksa, P, Rivera, L., Acosta, B., Arroba Basanta, M.L., Aziz, A., Cabanero, M.A., Chandrashekaran, V., Corsaro, B., Cousin, L., Diaz, A., Diez-Domingo, J., Dinleyici, E.C., Faust, S.N., Friel, D., Garcia-Sicilia, J., Go, G.D., Gonzales, M.L.A., Hughes, S.M., Jackowska, T., Kant, S., Lucero, M., Malvaux, L., Mares Bermudez, J., Martinon-Torres, F., Miranda, M., Montellano, M., Peix Sambola, M.A., Prymula, R., Puthanakit, T., Ruzkova, R., Sadowska-Krawczenko, I., Salamanca de la Cueva, I., Sokal, E., Soni, J., Szymanski, H., Ulied, A., Schuind, A., Jain, V.K. and Innis, B.L. (2018) Prevention of vaccine-matched and mismatched influenza in children aged 6–35 months: a multinational randomised trial across five influenza seasons. The Lancet Child & Adolescent Health, 338-349. (doi:10.1016/S2352-4642(18)30062-2).

Record type: Article

Abstract

Background

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.

Methods

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.

Findings

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.

Interpretation

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.

Funding

GlaxoSmithKline Biologicals SA.

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More information

Accepted/In Press date: 7 February 2018
e-pub ahead of print date: 5 March 2018
Published date: 6 March 2018

Identifiers

Local EPrints ID: 417883
URI: http://eprints.soton.ac.uk/id/eprint/417883
PURE UUID: 17a6d960-42c8-4852-aa97-a7bc6f2ce750
ORCID for S.N. Faust: ORCID iD orcid.org/0000-0003-3410-7642

Catalogue record

Date deposited: 16 Feb 2018 17:30
Last modified: 26 Nov 2021 05:09

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Contributors

Author: C. Claeys
Author: K. Zaman
Author: G. Dbaibo
Author: P. Li
Author: A. Izu
Author: P Kosalaraksa
Author: L. Rivera
Author: B. Acosta
Author: M.L. Arroba Basanta
Author: A. Aziz
Author: M.A. Cabanero
Author: V. Chandrashekaran
Author: B. Corsaro
Author: L. Cousin
Author: A. Diaz
Author: J. Diez-Domingo
Author: E.C. Dinleyici
Author: S.N. Faust ORCID iD
Author: D. Friel
Author: J. Garcia-Sicilia
Author: G.D. Go
Author: M.L.A. Gonzales
Author: S.M. Hughes
Author: T. Jackowska
Author: S. Kant
Author: M. Lucero
Author: L. Malvaux
Author: J. Mares Bermudez
Author: F. Martinon-Torres
Author: M. Miranda
Author: M. Montellano
Author: M.A. Peix Sambola
Author: R. Prymula
Author: T. Puthanakit
Author: R. Ruzkova
Author: I. Sadowska-Krawczenko
Author: I. Salamanca de la Cueva
Author: E. Sokal
Author: J. Soni
Author: H. Szymanski
Author: A. Ulied
Author: A. Schuind
Author: V.K. Jain
Author: B.L. Innis

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