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Lancet Child Adolesc Health
. 2026 May;10(5):352-363.
doi: 10.1016/S2352-4642(26)00009-X.
Efficacy, immunogenicity, and safety of a cell culture-derived quadrivalent influenza vaccine compared with a non-influenza vaccine in infants and children across five influenza seasons: a phase 3, multinational, observer-blind, randomised controlled trial
Airi Põder 1 , Anna Lisa Ong-Lim 2 , Doris Maribel Rivera Medina 3 , Khalequ Zaman 4 , Iryna Makedonska 5 , Marianne de Bruijn 6 , Vince Matassa 7 , Alexandre C Fortanier 6 , Esther Heijnen 6 , Matthew Hohenboken 8 , Deborah C Molrine 9
Affiliations
Background: The burden of influenza is high in children younger than 5 years, and vaccination is an effective strategy to reduce disease. We aimed to evaluate the efficacy and immunogenicity of a cell culture-derived quadrivalent inactivated influenza vaccine (QIVc), as well as its safety and tolerability, in infants and young children.
Methods: This phase 3, multinational, observer-blind, randomised controlled trial was conducted at 75 sites across 15 countries. Enrolled infants and children aged 6-47 months were randomly assigned (1:1) to receive QIVc containing 15 μg haemagglutinin from the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains or comparator MenC containing 10 μg of meningococcal group C polysaccharide conjugated to tetanus toxoid. Randomisation was done centrally by an interactive response technology system. Study staff administering vaccine were unmasked because the vaccines differed in physical appearance, whereas study participants, their parents or legally authorised representatives, and the study personnel responsible for efficacy, safety, and immunogenicity assessments were masked to the group assignment. QIVc and MenC groups followed the same vaccination schedule. Participants with an influenza vaccination history received one dose of QIVc or MenC on day 1. Participants in the QIVc group with no influenza vaccination history received a second QIVc dose on day 29 whereas participants in the MenC group with no influenza vaccination history received a placebo vaccine (saline) on day 29. To monitor for protocol-defined influenza-like illness and safety, participants were followed up via weekly telephone calls or scheduled clinic visits for at least 180 days after last vaccination. The primary efficacy endpoint was absolute vaccine efficacy against first-occurrence influenza more than 14 days after the last vaccination and until the end of the influenza season. Absolute vaccine efficacy was defined as the relative reduction in influenza infection rate in the QIVc group relative to the MenC group and based on first-occurrence RT-PCR-confirmed or culture-confirmed influenza antigenically similar to seasonal vaccine strain. Time-to-event methodology based on a proportional hazard model was used for efficacy analyses that included all participants who received at least one dose of study vaccine. The primary objective of efficacy was demonstrated if the lower limit of the two-sided (interim analysis-adjusted) 97·5% CI of vaccine efficacy was greater than 0%. Safety was evaluated in all participants randomly assigned and vaccinated and who provided at least one post-vaccination safety observation. Safety endpoints included the percentage of participants with solicited local and systemic AEs. The study is registered at ClinicalTrials.gov (NCT03932682) and EudraCT (2018-001857-29), and the study is complete.
Findings: Between May 13, 2019, and June 2, 2023, 5723 infants and children (2751 [48·1%] female; 2972 [51·9%] male; mean age 25·9 months [SD 11·9]) were randomly assigned to the QIVc group (n=2860) and MenC group (n=2863). 26 participants did not receive any vaccine, and six participants withdrew before the start of the surveillance period. First occurrence of RT-PCR-confirmed influenza occurred in 104 (3·6%) of 2856 participants in the QIVc group and 173 (6·1%) of 2835 participants in the MenC group; absolute vaccine efficacy was 41·3% (97·98% CI 21·6-56·0). First occurrence of culture-confirmed antigenically similar influenza occurred in 44 (1·5%) of 2856 participants in the QIVc group and 82 (2·9%) of 2835 participants in the MenC group; absolute vaccine efficacy was 46·9% (97·5% CI 19·2-65·1). No serious adverse events were deemed related to QIVc, and one serious adverse event of community-acquired pneumonia was deemed possibly related to the MenC vaccine by the investigator. Most solicited adverse reactions were mild or moderate in severity. Three deaths were reported during the study, none of which were deemed related to study vaccines.
Interpretation: The primary objective of efficacy was demonstrated for both first-occurrence RT-PCR-confirmed and first-occurrence culture-confirmed, antigenically similar influenza following an influenza-like illness more than 14 days after last vaccination. QIVc thus provided protection against influenza and had a clinically acceptable safety profile, supporting the benefit of QIVc in this paediatric population.
Funding: Seqirus UK.
. 2026 May;10(5):352-363.
doi: 10.1016/S2352-4642(26)00009-X.
Efficacy, immunogenicity, and safety of a cell culture-derived quadrivalent influenza vaccine compared with a non-influenza vaccine in infants and children across five influenza seasons: a phase 3, multinational, observer-blind, randomised controlled trial
Airi Põder 1 , Anna Lisa Ong-Lim 2 , Doris Maribel Rivera Medina 3 , Khalequ Zaman 4 , Iryna Makedonska 5 , Marianne de Bruijn 6 , Vince Matassa 7 , Alexandre C Fortanier 6 , Esther Heijnen 6 , Matthew Hohenboken 8 , Deborah C Molrine 9
Affiliations
- PMID: 41962984
- DOI: 10.1016/S2352-4642(26)00009-X
Background: The burden of influenza is high in children younger than 5 years, and vaccination is an effective strategy to reduce disease. We aimed to evaluate the efficacy and immunogenicity of a cell culture-derived quadrivalent inactivated influenza vaccine (QIVc), as well as its safety and tolerability, in infants and young children.
Methods: This phase 3, multinational, observer-blind, randomised controlled trial was conducted at 75 sites across 15 countries. Enrolled infants and children aged 6-47 months were randomly assigned (1:1) to receive QIVc containing 15 μg haemagglutinin from the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria strains or comparator MenC containing 10 μg of meningococcal group C polysaccharide conjugated to tetanus toxoid. Randomisation was done centrally by an interactive response technology system. Study staff administering vaccine were unmasked because the vaccines differed in physical appearance, whereas study participants, their parents or legally authorised representatives, and the study personnel responsible for efficacy, safety, and immunogenicity assessments were masked to the group assignment. QIVc and MenC groups followed the same vaccination schedule. Participants with an influenza vaccination history received one dose of QIVc or MenC on day 1. Participants in the QIVc group with no influenza vaccination history received a second QIVc dose on day 29 whereas participants in the MenC group with no influenza vaccination history received a placebo vaccine (saline) on day 29. To monitor for protocol-defined influenza-like illness and safety, participants were followed up via weekly telephone calls or scheduled clinic visits for at least 180 days after last vaccination. The primary efficacy endpoint was absolute vaccine efficacy against first-occurrence influenza more than 14 days after the last vaccination and until the end of the influenza season. Absolute vaccine efficacy was defined as the relative reduction in influenza infection rate in the QIVc group relative to the MenC group and based on first-occurrence RT-PCR-confirmed or culture-confirmed influenza antigenically similar to seasonal vaccine strain. Time-to-event methodology based on a proportional hazard model was used for efficacy analyses that included all participants who received at least one dose of study vaccine. The primary objective of efficacy was demonstrated if the lower limit of the two-sided (interim analysis-adjusted) 97·5% CI of vaccine efficacy was greater than 0%. Safety was evaluated in all participants randomly assigned and vaccinated and who provided at least one post-vaccination safety observation. Safety endpoints included the percentage of participants with solicited local and systemic AEs. The study is registered at ClinicalTrials.gov (NCT03932682) and EudraCT (2018-001857-29), and the study is complete.
Findings: Between May 13, 2019, and June 2, 2023, 5723 infants and children (2751 [48·1%] female; 2972 [51·9%] male; mean age 25·9 months [SD 11·9]) were randomly assigned to the QIVc group (n=2860) and MenC group (n=2863). 26 participants did not receive any vaccine, and six participants withdrew before the start of the surveillance period. First occurrence of RT-PCR-confirmed influenza occurred in 104 (3·6%) of 2856 participants in the QIVc group and 173 (6·1%) of 2835 participants in the MenC group; absolute vaccine efficacy was 41·3% (97·98% CI 21·6-56·0). First occurrence of culture-confirmed antigenically similar influenza occurred in 44 (1·5%) of 2856 participants in the QIVc group and 82 (2·9%) of 2835 participants in the MenC group; absolute vaccine efficacy was 46·9% (97·5% CI 19·2-65·1). No serious adverse events were deemed related to QIVc, and one serious adverse event of community-acquired pneumonia was deemed possibly related to the MenC vaccine by the investigator. Most solicited adverse reactions were mild or moderate in severity. Three deaths were reported during the study, none of which were deemed related to study vaccines.
Interpretation: The primary objective of efficacy was demonstrated for both first-occurrence RT-PCR-confirmed and first-occurrence culture-confirmed, antigenically similar influenza following an influenza-like illness more than 14 days after last vaccination. QIVc thus provided protection against influenza and had a clinically acceptable safety profile, supporting the benefit of QIVc in this paediatric population.
Funding: Seqirus UK.