Background: The development of vaccines against pandemic influenza viruses for use in children is a public health priority.
Methods: In this phase II, randomized, open study, the immunogenicity and reactogenicity of H5N1 A/Vietnam/1194/2004 (NIBRG-14) (clade 1) prepandemic influenza vaccine were assessed in children aged 3 to 5 and 6 to 9 years. Children were randomized to receive 2 doses, given 21 days apart, of A/Vietnam/1194/2004 vaccine containing 1.9 μg or 3.75 μg hemagglutinin antigen (HA), adjuvanted with a tocopherol-based oil-in-water emulsion (AS03) containing 11.86 mg (AS03A) or 5.93 mg (AS03B) tocopherol. Control groups received 2 doses of trivalent influenza vaccine (TIV). Humoral immune responses, reactogenicity, and safety were the primary outcome measures; cross-reactivity and cell-mediated responses were also assessed (NCT00502593).
Results: Between 49 and 51 children in each age stratum (aged 3–5 and 6–9 years) received H5N1 vaccine, and between 17 and 18 children in each age stratum received TIV. After the second dose, recipients of H5N1 vaccine (1.9 μg HA/AS03B, 3.75 μg HA/AS03B, and 3.75 μg HA/AS03A) achieved humoral antibody titers against the vaccine-homologous strain, which fulfilled the United States influenza vaccines licensure criteria for immunogenicity. With the exception of 1 child, there were no H5N1 immune responses in children who received TIV. The most frequent injection-site event was pain in all groups, and the H5N1 vaccine had a clinically acceptable reactogenicity and safety profile. Exploratory analyses in children aged 3 to 5 years indicated that the induction of CD4+ T-cell responses polarized in favor of a T-helper 1 profile.
Conclusions: The results showed that 2 doses of AS03-adjuvanted H5N1 influenza vaccine at antigen-sparing doses of 1.9 μg or 3.75 μg HA elicited broad and persistent immune responses with acceptable reactogenicity, and without safety concerns, in children aged 3 to 9 years.