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

Abstract

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.

• Authors: Robert B Belshe, Sharon E Frey, Irene Graham, Mark J Mulligan, Srilatha Edupuganti, Lisa A Jackson, Anna Wald, Gregory Poland, Robert Jacobson, Harry L Keyserling, Paul Spearman, Heather Hill, Mark Wolff, National Institute of Allergy and Infectious Diseases-Funded Vaccine and Treatment Evaluation Units
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 203 Issue 5 Pg. 666-73 (Mar 01 2011) ISSN: 1537-6613 [Electronic] United States
• PMID: 21282194 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies, Viral
• Influenza Vaccines
• Vaccines, Subunit

Topics

• Adolescent
• Adult
• Antibodies, Viral (blood)
• Antigenic Variation
• Drug Administration Schedule
• Female
• Humans
• Immunization, Secondary
• Influenza A Virus, H5N1 Subtype (immunology)
• Influenza A virus (immunology)
• Influenza Vaccines (administration & dosage, adverse effects, immunology, standards)
• Influenza, Human (blood, prevention & control)
• Male
• Middle Aged
• Vaccines, Subunit (administration & dosage, adverse effects, immunology, standards)
• Young Adult