title: Vaccine for prevention of mild and moderate-to-severe influenza in children.
abstract: BACKGROUND
  Commonly used trivalent vaccines contain one influenza B virus lineage and may be ineffective against viruses of the other B lineage. We evaluated the efficacy of a candidate inactivated quadrivalent influenza vaccine (QIV) containing both B lineages.
  
  
  METHODS
  In this multinational, phase 3, observer-blinded study, we randomly assigned children 3 to 8 years of age, in a 1:1 ratio, to receive the QIV or a hepatitis A vaccine (control). The primary end point was influenza A or B confirmed by real-time polymerase chain reaction (rt-PCR). Secondary end points were rt-PCR-confirmed, moderate-to-severe influenza and rt-PCR-positive, culture-confirmed influenza. The vaccine efficacy and the effect of vaccination on daily activities and utilization of health care resources were assessed in the total vaccinated cohort (2584 children in each group) and the per-protocol cohort (2379 children in the QIV group and 2398 in the control group).
  
  
  RESULTS
  In the total vaccinated cohort, 62 children in the QIV group (2.40%) and 148 in the control group (5.73%) had rt-PCR-confirmed influenza, representing a QIV efficacy of 59.3% (95% confidence interval [CI], 45.2 to 69.7), with efficacy against culture-confirmed influenza of 59.1% (97.5% CI, 41.2 to 71.5). For moderate-to-severe rt-PCR-confirmed influenza, the attack rate was 0.62% (16 cases) in the QIV group and 2.36% (61 cases) in the control group, representing a QIV efficacy of 74.2% (97.5% CI, 51.5 to 86.2). In the per-protocol cohort, the QIV efficacy was 55.4% (95% CI, 39.1 to 67.3), and the efficacy against culture-confirmed influenza 55.9% (97.5% CI, 35.4 to 69.9); the efficacy among children with moderate-to-severe influenza was 73.1% (97.5% CI, 47.1 to 86.3). The QIV was associated with reduced risks of a body temperature above 39°C and lower respiratory tract illness, as compared with the control vaccine, in the per-protocol cohort (relative risk, 0.29 [95% CI, 0.16 to 0.56] and 0.20 [95% CI, 0.04 to 0.92], respectively). The QIV was immunogenic against all four strains. Serious adverse events occurred in 36 children in the QIV group (1.4%) and in 24 children in the control group (0.9%).
  
  
  CONCLUSIONS
  The QIV was efficacious in preventing influenza in children. (Funded by GlaxoSmithKline Biologicals; ClinicalTrials.gov number, NCT01218308.).
authors: The authors' affiliations are listed in the Appendix.
authors: Varsha K
authors: VK
authors: Jain
authors: Luis
authors: L
authors: Rivera
authors: Khalequ
authors: K
authors: Zaman
authors: Roberto A
authors: RA
authors: Espos
authors: Chukiat
authors: C
authors: Sirivichayakul
authors: Beatriz P
authors: BP
authors: Quiambao
authors: Doris M
authors: DM
authors: Rivera-Medina
authors: Pirunghul
authors: P
authors: Kerdpanich
authors: Mehmet
authors: M
authors: Ceyhan
authors: Ener C
authors: EC
authors: Dinleyici
authors: Alejandro
authors: A
authors: Cravioto
authors: Mohammed
authors: M
authors: Yunus
authors: Pornthep
authors: P
authors: Chanthavanich
authors: Kriengsak
authors: K
authors: Limkittikul
authors: Zafer
authors: Z
authors: Kurugol
authors: Emre
authors: E
authors: Alhan
authors: Adrian
authors: A
authors: Caplanusi
authors: Serge
authors: S
authors: Durviaux
authors: Philippe
authors: P
authors: Boutet
authors: Opokua
authors: O
authors: Ofori-Anyinam
authors: Vijayalakshmi
authors: V
authors: Chandrasekaran
authors: Ghassan
authors: G
authors: Dbaibo
authors: Bruce L
authors: BL
authors: Innis
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D006385:Hemagglutination Inhibition Tests; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D009981:Influenza B virus / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D007252:Influenza Vaccines / Q000009:adverse effects / Q000276:immunology*; D007251:Influenza, Human / Q000145:classification / Q000175:diagnosis / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D016016:Proportional Hazards Models; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D016037:Single-Blind Method; D015164:Vaccines, Inactivated / Q000276:immunology
chemical_list: D007252:Influenza Vaccines; D015164:Vaccines, Inactivated