An adjuvant trivalent inactivated influenza vaccine in an oil-and-water emulsion that augments the immune response was found effective in a field trial of 4,707 German and Finnish children, according to a report in the Oct. 13 issue of the New England Journal of Medicine.
The novel vaccine showed 86% efficacy against all circulating viral strains of influenza during the 2 years of the trial, and 89% efficacy against vaccine-matched strains. In contrast, efficacy rates for the standard trivalent inactivated flu vaccine, which is known to be poorly immunogenic in children, were 43% and 45%, respectively, said Dr. Timo Vesikari of the University of Tampere (Finland) and his associates.
The oil-in-water emulsion (MF59), which enhances the immune response when combined with vaccine antigens, has been used since 1997 in the influenza vaccine for older adults, and has been licensed in 27 countries. In an earlier study, Dr. Vesikari and his colleagues reported that it induced a greater immune response in children aged 6-36 months than did the standard vaccine formulation.
They now report the results of a phase III trial in 654 children in Germany in year 1, as well as 2,104 children in Germany and 1,949 in Finland during year 2. These study subjects were aged 6-71 months of age.
The study participants were randomly assigned to one of three groups: the novel vaccine group (1,941 patients), those receiving the standard subunit trivalent inactivated vaccine that is poorly immunogenic in children (1,773 patients), or a control group receiving noninfluenza vaccine (993 patients).
The vaccines were administered in two doses, 1 month apart.
The absolute efficacy of the novel vaccine for both influenza seasons was 86% against all strains and 89% against vaccine-matched strains and the influenza A(H3N2) virus. In contrast, the standard vaccine had an efficacy of 43% against all strains and 45% against vaccine-matched strains and the H3N2 virus.
When the data were broken down by patient age, the novel vaccine showed efficacy against 64% of all strains and 68% of matched strains among children aged 6-35 months, and against 86% of all strains and 91% of matched strains among children aged 36-71 months, the investigators said (N. Engl. J. Med. 2011;365:1406-16).
Moreover, the study subjects frequently showed an immune response after only the first dose of the novel vaccine, but not so with the standard or control vaccines.
At ages 6-35 months, rates of seroprotection against influenza A(H1N1) and H3N2 strains after one dose were 92% and 95%, respectively, with the novel vaccine. The corresponding rates of seroprotection after one dose of the standard vaccine were only 20% and 12%, respectively.
In children aged 36-71 months of age, these proportions after one dose were 100% and 97% for the novel vaccine, compared with 63% and 60% for the standard vaccine.
Vaccine-related adverse events were generally mild to moderate and were similar across the three vaccine groups in the younger patients. In older patients aged 36-71 months, "systemic reactions, including mild fever, were slightly more frequent after receipt of the [novel] vaccine, as compared with the other vaccines, but these reactions were mostly mild and of short duration," Dr. Vesikari and his associates said.
In all, 13 children were withdrawn from the study because of serious adverse events, which were distributed evenly across the three study groups.
This study was funded by Novartis Vaccines. Novartis employees also designed and conducted the study and analyzed the data. Dr. Vesikari and his associates reported ties to Astra Zeneca, GlaxoSmithKline, MedImmune, Merck, Pfizer, Sanofi Pasteur, SPMSD, and Wyeth.