Safety and Immunogenicity of Influenza A H5 Subunit Vaccines: Effect of Vaccine Schedule and Antigenic Variant

• Published in: The Journal of infectious diseases Vol. 203; no. 5; pp. 666 - 673
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2011
• Subjects: Adolescent; Adult; Antibodies; Antibodies, Viral - blood; Antigenic Variation; Antigens; Applied microbiology; Biological and medical sciences; Dosage; Drug Administration Schedule; Female; Fundamental and applied biological sciences. Psychology; H5N1 subtype influenza A virus; Health care administration; Humans; Immune response; Immunization, Secondary; Infectious diseases; Influenza A virus; Influenza A virus - immunology; Influenza A Virus, H5N1 Subtype - immunology; Influenza Vaccines - administration & dosage; Influenza Vaccines - adverse effects; Influenza Vaccines - immunology; Influenza Vaccines - standards; Influenza, Human - blood; Influenza, Human - prevention & control; Major and Brief Reports; Male; Medical sciences; Microbiology; Middle Aged; Pandemics; Vaccination; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Subunit - administration & dosage; Vaccines, Subunit - adverse effects; Vaccines, Subunit - immunology; Vaccines, Subunit - standards; Viruses; Young Adult; Vietnam; Indonesia; Infection; Influenza A; Vaccine; Immunogenicity; Subunit; Viral disease
• ISSN: 0022-1899; 1537-6613; 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiq093

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