New England Journal of Medicine
January 2, 2014  Vol. 370 No. 1
http://www.nejm.org/toc/nejm/medical-journal
[No relevant content]

December 26, 2013  Vol. 369 No. 26
Original Article
Vaccine for Prevention of Mild and Moderate-to-Severe Influenza in Children
Varsha K. Jain, M.D., M.P.H., Luis Rivera, M.D., Khalequ Zaman, M.B., B.S., Ph.D., Roberto A. Espos, Jr., M.D., M.H.S.A., Chukiat Sirivichayakul, M.D., Beatriz P. Quiambao, M.D., Doris M. Rivera-Medina, M.D., Pirunghul Kerdpanich, M.D., Mehmet Ceyhan, M.D., Ener C. Dinleyici, M.D., Alejandro Cravioto, M.D., Ph.D., Mohammed Yunus, M.B., B.S., Pornthep Chanthavanich, M.D., Kriengsak Limkittikul, M.D., Zafer Kurugol, M.D., Ph.D., Emre Alhan, M.D., Adrian Caplanusi, M.D., Ph.D., Serge Durviaux, B.A., Philippe Boutet, D.V.M., Ph.D., Opokua Ofori-Anyinam, Ph.D., Vijayalakshmi Chandrasekaran, M.Sc., Ghassan Dbaibo, M.D., and Bruce L. Innis, M.D.
N Engl J Med 2013; 369:2481-2491December 26, 2013DOI: 10.1056/NEJMoa1215817
http://www.nejm.org/doi/full/10.1056/NEJMoa1215817

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.)