A prime-boost flu vaccination strategy proved effective in children and adolescents in an open-label phase III trial conducted by the vaccine manufacturer and reported online in the Pediatric Infectious Disease Journal.
This proof-of-concept result suggests that at the outbreak of the next flu pandemic, immediate priming with two doses of a subtype-matched flu vaccine, followed by boosting once a strain-matched vaccine becomes available, will offer the pediatric population better protection than simply waiting for adequate quantities of the strain-matched vaccine to be developed and marketed.
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It is impossible to predict which specific viral strain will cause the next flu pandemic, but H5N1 is considered a likely candidate virus, “to the extent that vaccine manufacturers and regulatory authorities are actively developing H5N1 vaccines” for all age groups, said Dr. Patricia Izurieta of GlaxoSmithKline Vaccines, Belgium, and her associates.
Waiting for a pandemic to begin and then producing strain-specific vaccines could take as long as 6 months, and even then supplies probably would be limited. Experts have theorized that preemptive “priming” with already stockpiled H5N1 vaccines immediately after a pandemic begins may provide broad cross-protection that could mitigate the intensity of the subsequent pandemic, potentially reducing morbidity, mortality, and viral transmission.
To test this theory, Dr. Izurieta and her associates mimicked a potential flu pandemic by priming children and adolescents with two doses of an H5N1-AS03 vaccine, giving a booster dose of a specific H5N1 strain at 6 months, and assessing antibody response to all the vaccinations through 12 months. (Assessing actual vaccine efficacy was impossible because it would be unethical to determine this by exposing children to a flu virus.)
A total of 520 participants at a single medical center in the Philippines who were aged 3-18 years (mean age, 9 years) were assigned to two intervention groups and two control groups. Approximately half of these children and adolescents received the intervention – two priming doses of A/Indonesia/05/2005/H5N1-AS03B vaccine – while the control subjects received a single dose of hepatitis A vaccine. At day 182, half of the primed and half of the unprimed participants then received a booster dose of A/turkey/Turkey/01/2005-H5N1-As03B, while the remainder received the hepatitis A vaccine.
Compared with no priming, priming afforded superior seroconversion and putative seroprotection against the second, specific strain of H5N1. This robust protective effect was seen within 10 days after vaccination, occurred across all ages, and persisted through 12 months of follow-up, the investigators said (Ped Infect Dis J. 2015 Nov 6. [doi: 10.1097/INF.0000000000000968]).
Adverse events within 7 days of the priming vaccinations developed in 68%-76% of the intervention group, compared with only 37%-64% of the control group. Adverse events within 7 days of the booster vaccinations developed in 69% of the intervention group, compared with only 40% of the control group. The most common adverse events were upper respiratory tract infection (20% vs 14%), nasopharyngitis (4% vs 3%), and rhinitis (3% in both study groups). The most serious adverse events affected two children and were classified as grade 3.
The study results suggest that a prime-boost strategy can induce broad and long-lasting immunity and could be effectively employed in this age group in the prepandemic setting, Dr. Izurieta and her associates reported.
This trial was funded by GlaxoSmithKline, which also was involved in the design and conduct of the study, the data analysis, and the writing and publishing of the report. Dr. Izurieta and two of her associates are employed by GSK.