Prime-boost vaccination using influenza A H5N1 vaccines

Vaccination offers the best method for protecting the general population against an influenza pandemic, but has limitations. The output from the vaccine industry will be insufficient to meet demand, and the time required to make a pandemic vaccine means that it will be scarce and possibly unavailable during the first wave of the pandemic. The new, deadly H5N1 influenza virus, when given as an ordinary vaccine, is also very poor at stimulating protective antibody responses. Our study explores the possibility of ?priming? people with small quantities of an H5 adjuvanted vaccine (which contains a substance to enhance the body?s immune response) before a pandemic with the expectation that the body will develop a more vigorous immune response to a pandemic vaccine when it became available. This would enable scarce supplies of pandemic vaccine to be given more efficiently, with protection of more people more rapidly

The Leicester-NIBSC-HPA Influenza Consortium has a strong research platform on reverse genetics, vaccine standardisation, evaluation of candidate pandemic vaccines in humans and animals, and serology, notably virus neutralisation. It is uniquely placed in Europe. We propose to apply our expertise to address pandemic pre-vaccination (prime-boosting) strategies for H5N1 influenza. MF59 oil in water emulsion is a potent adjuvant for human H5 and H9 vaccines. This project builds on previous and ongoing work by the Consortium with H5 and H9 vaccines in animals and man, vaccine adjuvants, and dose-sparing strategies. The objective is examine the use of MF59 adjuvanted influenza A/Vietnam/1194/2004 (H5N1) [RG14] vaccine as a pre-pandemic vaccine to prime for later vaccination with low doses of plain or adjuvanted vaccines containing a drifted H5 antigenic variant. Using a factorial design, we will evaluate the ability of one or two 7.5 microgram doses of MF59 adjuvanted RG14 vaccine to prime for protective antibody responses to a drift variant (e.g., A/turkey/Turkey/1/2005 (H5N1)), administered 12 months later, as plain or MF-59 adjuvanted vaccine, in 3.75 or 7.5 microgram doses. We will measure the kinetics of the antibody response to ?boosters? of plain and adjuvanted vaccine, to the vaccine strains and antigenic variants. Parallel studies will be done in laboratory models. Protection afforded by (a) ?priming?, and (b) ?boosting? will be compared in laboratory models.