Cell culture (Vero cell) derived whole-virus non-adjuvanted H5N1 influenza vaccine induces long-lasting cross-reactive memory immune response: homologous or heterologous booster response following two dose or single dose priming.

ABSTRACT

BACKGROUND: Influenza pandemic preparedness involves priming of the population with pre-pandemic vaccines. Such vaccines should be well tolerated and induce a long-lasting immunological memory that can effectively be boosted with a single dose of pandemic vaccine once available. The presented studies assessed different prime-boost regimens with a Vero cell-derived whole virus non-adjuvanted H5N1 vaccine. METHODS: In one study, 281 healthy adult (18-59 years) and 280 elderly (≥ 60 years) subjects received two vaccinations, 21 days apart, with Vero cell-derived whole virus non-adjuvanted H5N1 vaccine (7.5 µg HA Antigen A/Vietnam/1203/2004) followed by a 6, 12-15, or 24 month booster (7.5 or 3.75µg A/Indonesia/05/2005 or A/Vietnam/1203/2004). In the other study, 230 healthy adults (18-59 years) received single dose priming (7.5 µg A/Vietnam/1203/2004) followed by a 12 month booster (7.5 or 3.75 µg A/Indonesia/05/2005). Antibody responses were assessed by microneutralization (MN) and single radial hemolysis (SRH) assay. Vaccine safety was assessed throughout. RESULTS: Two dose priming was equally immunogenic in adults and the elderly >72% of subjects in each population achieved MN titers ≥ 120 after the second vaccination. Booster vaccinations at 6, 12-15, and 24 months induced substantial antibody increases to both strains after a 7.5 µg A/Indonesia/05/2005 booster, 93-95% of adults and 72-84% of the elderly achieved MN titers ≥ 120 against this strain. Homologous and heterologous booster responses were higher in the 7.5µg dose group than in the 3.75 µg dose group. Booster responses following single dose priming were similar; a 7.5 µg booster dose induced homologous MN titers ≥ 120 in 93% of subjects. CONCLUSIONS: A Vero cell derived whole virus non-adjuvanted H5N1 influenza vaccine is well tolerated and induces long-lasting cross-clade immunological memory that can be effectively boosted 1-2 years after two dose or single dose priming, supporting its suitability for pre-pandemic vaccination.