Vaccine for Prevention of Mild and Moderate-to-Severe Influenza in Children


Varsha K. Jain, M.D., M.P.H., GlaxoSmithKline Vaccines
Luis Rivera, M.D., Department of Neo - natal-Perinatal Medicine, Hospital Maternidad Nuestra Señora de la Altagracia
Khalequ Zaman, M.B., B.S., Ph.D., Centre for Child and Adolescent Health, International Center for Diarrheal Disease Research
Roberto A. Espos, Jr., M.D., M.H.S.A., Department of Pediatrics, De La Salle Health Sciences Institute and De La Salle College of Medicine
Chukiat Sirivichayakul, M.D., Department of Tropical Pediatrics, Mahidol University
Beatriz P. Quiambao, M.D., Clinical Research Division, Research Institute for Tropical Medicine
Doris M. Rivera-Medina, M.D., Clinical Research Department, Organización para el Desarrollo y la Investigación Salud en Honduras (ODISH)
Pirunghul Kerdpanich, M.D., Department of Infectious Pediatrics, Phramongkutklao Hospital of the Royal Thai Army
Mehmet Ceyhan, M.D., Department of Pediatrics and Infectious Diseases, Hacettepe University
Ener C. Dinleyici, M.D., Department of Pediatric Intensive Care and Infectious Disease Unit
Alejandro Cravioto, M.D., Ph.D., GlaxoSmithKline Vaccines
Mohammed Yunus, M.B., B.S., Center for Child and Adolescent Health
Pornthep Chanthavanich, M.D., Department of Tropical Pediatrics, Mahidol University
Kriengsak Limkittikul, M.D., Department of Tropical Pediatrics, Mahidol University
Zafer Kurugol, M.D., Ph.D., Department of Pediatrics, Ege University Faculty of Medicine
Emre Alhan, M.D., Department of Pediatrics, Division of Pediatric Infectious Disease, Cukurova University
Adrian Caplanusi, M.D., Ph.D., International Center for Diarrheal Disease Research
Serge Durviaux, B.A., GlaxoSmithKline Vaccines
Philippe Boutet, D.V.M., Ph.D., GlaxoSmithKline Vaccines
Opokua Ofori-Anyinam, Ph.D., GlaxoSmithKline Vaccines
Vijayalakshmi Chandrasekaran, M.Sc., GlaxoSmithKline Vaccines
Ghassan Dbaibo, M.D., Department of Pediatrics and Adolescent Medicine, American University of Beirut Medical Center
Bruce L. Innis, M.D., GlaxoSmithKline Vaccines

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The New England Journal of Medicine


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.)

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