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

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 ≥ 1:20 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 ≥ 1:20 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 ≥ 1:20 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.