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

Division of Infectious Diseases and Immunology, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA.
The Journal of Infectious Diseases (Impact Factor: 6). 03/2011; 203(5):666-73. DOI: 10.1093/infdis/jiq093
Source: PubMed


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).
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.
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.
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.

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    • "Immunogenicity studies of H5 influenza vaccines have examined intrasubtypic heterologous immunity to drifted viruses of other H5N1 clades and subclades produced by priming strains, and immunity produced by heterologous boosting with drifted H5N1 strains 6 months–8 years after the priming series [5] [6] [7] [8] [9] [10] [11] [12]. Although some of these studies involve small sample sizes, they provide evidence that priming followed by heterologous boosting with a drifted strain can induce cross-protective antibody responses, with oil-in-water adjuvanted vaccines producing the highest titers and unadjuvanted vaccines being poor immunogens [13]. "
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