Assessment of Prime-boost Vaccination Using an AS03B-adjuvanted Influenza A (H5N1) Vaccine: A Randomized Trial in Children of Three to Less Than Eighteen Years of Age.

BACKGROUND

Heterologous prime-boost vaccination is a pandemic response strategy utilizing subtype-matched vaccine at pandemic onset followed by strain-matched vaccine once available. Persistence of immune response and safety of influenza A (H5N1) vaccine adjuvanted with adjuvant system containing α-tocopherol and squalene in an oil-in-water emulsion (AS03B) were evaluated.

METHODS

An open phase 3 active-controlled study (www.clinicaltrials.gov NCT01379937) assessed immunogenicity and reactogenicity of a heterologous booster dose of A/turkey/Turkey/1/2005-H5N1-AS03B in children 3 to <18 years of age, given 6 months after 2-dose priming with A/Indonesia/05/2005-H5N1-AS03B (H5N1(2) -H5N1 group) compared with a single dose of A/turkey/Turkey/1/2005-H5N1-AS03B in unprimed subjects (hepatitis A vaccine (HAV)-H5N1 group). Hemagglutinin inhibition responses and microneutralization antibodies were assessed to 6 months after booster vaccination.

RESULTS

Hemagglutinin inhibition antibody responses against A/turkey/Turkey/1/2005-H5N1 were superior in the H5N1(2)-H5N1 versus the hepatitis A vaccine-H5N1 group overall and in each age strata (3 to <10 and 10 to <18 years). Anamnestic immune responses were demonstrated against vaccine-homologous/heterologous strains in the H5N1(2)-H5N1 group. Injection site pain and fever increased with consecutive doses for children <6 years (H5N1(2)-H5N1). Immune responses to vaccine-homologous/heterologous strains persisted to 6 months after booster vaccination in the H5N1(2)-H5N1 group.

CONCLUSIONS

Heterologous H5N1-AS03B-adjuvanted booster vaccination in children/adolescents was immunogenic for vaccine-homologous and heterologous strains following 2-dose priming, with immune persistence for at least 6 months. Prime-boost strategies using H5N1-AS03 could be effectively employed in this age group.