Safety and immunogenicity of influenza A H5 subunit vaccines: effect of vaccine schedule and antigenic variant.

Publication Type
Journal Article
Year of Publication
Belshe, Robert B; Frey, Sharon E; Graham, Irene; Mulligan, Mark J; Edupuganti, Srilatha; Jackson, Lisa A; Wald, Anna; Poland, Gregory; Jacobson, Robert; Keyserling, Harry L; Spearman, Paul; Hill, Heather; Wolff, Mark; National Institute of Allergy and Infectious Diseases-Funded Vaccine and Treatment Evaluation Units
J Infect Dis
Date Published
2011 Mar 01
Adolescent; Adult; Antibodies, Viral; Antigenic Variation; Drug Administration Schedule; Female; Humans; Immunization, Secondary; Influenza A Virus; Influenza A Virus, H5N1 Subtype; Influenza Vaccines; Influenza, Human; Male; Middle Aged; Vaccines, Subunit; Young Adult

BACKGROUND: The current US national stockpile of influenza H5 vaccine was produced using the antigen from the strain A/Vietnam/1203/2004 (a clade 1 H5 virus). Recent H5 disease has been caused by antigenically divergent H5 viruses, including A/Indonesia/05/2005 (a clade 2 H5 virus).

METHODS: The influence of schedule on the antibody response to 2 doses of H5 vaccines (one a clade 1 hemagglutinin protein [HA] vaccine and one a clade 2 HA vaccine) containing 90 μg of antigen was evaluated in healthy adults 18-49 years of age.

RESULTS: Two doses of vaccine were required to induce antibody titers ≥ 1:10 in most subjects. Accelerated schedules were immunogenic, and antibody developed after vaccinations on days 0 and 7, 0 and 14, and 0 and 28, with the day 0 and 7 schedule inducing lower titers than those induced with the other schedules. With mixed vaccine schedules of clade 1 followed by clade 2 vaccine administration, the first vaccination primed for a heterologous boost. The heterologous response was improved when the second vaccination was given 6 months after the first, compared with the response when the second vaccination was given after an interval of 1 month.

CONCLUSIONS: An accelerated vaccine schedule of injections administered at days 0 and 14 was as immunogenic as a vaccine schedule of injections at days 0 and 28, but both schedules were inferior to a vaccine schedule of injections administered at 0 and 6 months for priming for heterologous vaccine boosting. Clinical Trial Registry Number: NCT00703053.