Double-Dose Influenza Vaccine Safe, Effective in Young Children

In young children, administering the inactivated quadrivalent influenza vaccine (IIV4) at twice the standard dose approved in the United States may offer better protection against influenza B without additional adverse effects, according to a study published in the Journal of the Pediatric Infectious Diseases Society.

In the United States, the approved dose of IIV4 in children 3 years of age and older is 0.5 mL, which contains 15 µg of hemagglutinin (HA) per virus strain. The 0.25-mL dose, which contains 7.5 µg of HA per virus strain, is the only dose approved in children between 6 months and 3 years of age in the United States. However, both the 15-µg dose and the 7.5-µg dose are licensed for use in the younger age group in several other countries.

In the 1970s, when the whole-virus vaccine was the only influenza vaccine available, the 7.5-µg reduced dose was used in children younger than 3 years of age to decrease vaccine-related reactogenicity. But not all young children mount a sufficient immune response to the reduced dose. In addition, the split-virus vaccines used today have better tolerability than whole-virus vaccines, raising the question of whether the higher 15-µg dose may be more effective than the 7.5-µg dose while exhibiting a similar adverse event profile.

Researchers evaluated whether administering double-dose IIV4 to children younger than 3 years of age improved protection against influenza B without increasing adverse events in a phase 3 trial.

In a phase 3, randomized, observer-blind trial ( Identifier: NCT02242643), double-dose IIV4 (0.5 mL, 15 μg HA per influenza strain) was compared with standard-dose IIV4 (0.25 mL, 7.5 μg per strain) in 4465 children between 6 to 35 months of age.

The immunogenicity of double-dose IIV4 was noninferior to that of standard-dose IIV4 for all vaccine strains. A post hoc analysis found that the double dose had superior immunogenicity to both vaccine B strains compared with the standard dose in children age 6 to 17 months and in all vaccine-unprimed children.

The most common adverse event was pain at the injection site, which was similar (approximately 40%) in both treatment groups. No significant difference was found between the groups for fever 2 days following vaccination. Rates of serious adverse events, including febrile seizures, were also similar in both groups.

“In conclusion, a double-dose IIV4 may afford greater protection in young children against influenza B. Increased protection against influenza B, a potentially serious and life-threatening illness particularly in young children, would be a beneficial clinical outcome,” the researchers wrote.

“Use of the same vaccine dose for all eligible ages would also simplify the annual influenza vaccine campaign and reduce cost and logistic complexity. This study provides evidence to support a change in clinical practice to use a double-dose IIV4 (15 μg per antigen) in all children 6 months of age and older, once that dosing for a vaccine product has been approved,” they added.

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Jain VK, Domachowske JB, Wang L, et al. Time to change dosing of inactivated quadrivalent influenza vaccine in young children: evidence from a phase III, randomized, controlled trial [published online January 6, 2017]. J Pediatric Infect Dis Soc. doi: 10.1093/jpids/piw068