An inactivated quadrivalent influenza vaccine showed an overall efficacy of 55% against influenza A or B of any severity in an industry-sponsored phase III clinical trial involving children aged 3-8 years, which was reported online Dec. 11 in the New England Journal of Medicine.
The vaccine was most useful, with an efficacy of approximately 70%, against moderate to severe influenza. This is "a potentially important endpoint associated with the highest clinical, social, and economic burden" of disease, said Dr. Varsha K. Jain of GlaxoSmithKline Vaccines, King of Prussia, Pa., and his associates.
Amanda Mills/CDC
A recent study showed an inactivated quadrivalent flu vaccine showed an overall efficacy of 55% against influenza A or B and an efficacy of 70% against moderate to severe influenza.
Participants in the randomized controlled trial were healthy children treated at 15 medical centers in Bangladesh, the Dominican Republic, Honduras, Lebanon, Panama, the Philippines, Thailand, and Turkey. The mean age was 5.4 years, and there were approximately equal numbers of boys and girls.
The 5,168 participants were randomly assigned to receive either the quadrivalent flu vaccine (2,584 children) or the hepatitis A vaccine as a control condition (2,584 children), and were followed for 6-8 months for the development of influenza-like illness. Influenza A or B was confirmed by polymerase chain reaction (PCR) assay of nasal or throat swabs.
The primary endpoint of the study was the development of influenza A or B of any severity during follow-up. A total of 62 children (2.4%) in the vaccine group and 148 (5.7%) in the control group developed influenza, a significant difference.
In a per-protocol analysis involving a subset of 768 children, 58 participants (2.4%) in the flu vaccine group and 128 (5.3%) in the control group developed influenza, also a significant difference.
"The study met its primary objective by showing that the efficacy of the quadrivalent influenza vaccine against any case of PCR-confirmed influenza was 59.3% in the total vaccinated cohort and 55.4% in the per-protocol cohort," Dr. Jain and his associates reported (N. Engl. J. Med. 2013 Dec. 11 [doi: 10.1056/NEJMoa1215817]).
In a further analysis of the data, cases of influenza were categorized as either mild or moderate to severe. The vaccine showed an efficacy of 74.2% against moderate to severe disease among children in the total study cohort, and an efficacy of 73.1% against moderate to severe disease among children in the per-protocol subset.
In a post hoc exploratory analysis, the quadrivalent flu vaccine "was associated with an 80% reduction in the rate of lower respiratory tract illness (the most common serious outcome of influenza) and a 70% reduction in the rate of body temperature above 39 C, as compared with the control vaccine," the investigators said.
Serious adverse events occurred in 1.4% of the flu vaccine group and 0.9% of the control group, a nonsignificant difference. "There were no notable differences between the flu vaccine group and the control group with respect to safety endpoints, except that pain at the injection site was reported more frequently in the flu vaccine group," Dr. Jain and his associates said.
Until now, the evidence from randomized trials in support of the use of inactivated influenza vaccines among healthy children has been limited. This study provides evidence of the quadrivalent vaccine’s efficacy and safety, they added.
The quadrivalent vaccine contained strains of influenza A/California/7/2009 (H1N1), A/Victoria/210/2009 (H3N2), B/Brisbane/60/2008 (Victoria), and B/Florida/4/2006 (Yamagata).
This trial was funded by the vaccine manufacturer, GlaxoSmithKline. Dr. Jain and some of his associates are employed by GlaxoSmithKline. Dr. Jain’s associates also reported ties to Sanofi Pasteur, Novartis, and other companies.