Immunogenicity and safety of a novel AS03(A)-adjuvanted H1N1 2009 pandemic influenza vaccine in adults in Japan.

BACKGROUND AND OBJECTIVES: This study evaluated the immunogenicity and safety of a novel H1N1 2009 pandemic vaccine(A/California/7/2009) in Japanese adults. RESULTS: Following Dose 1, seroprotection rate (HI titre ≥1:40) was 95%, seroconversion rate was 94% and the geometric mean titre (GMT) was 230.3 (geometric mean fold rise [GMFR]: 26.3). Following Dose 2, seroprotection rate as well as seroconversion rate were 100%; HI antibody GMT rose to 485 (GMFR: 55.4). European and United States regulatory acceptance criteria for immunogenicity were met and exceeded following each dose of the vaccine. Solicited symptoms recorded during the 7-day post-vaccination follow-up period were of mild to moderate intensity (Grade 3: ≤4% of subjects). The most frequently reported solicited symptoms after both doses were pain at the injection site, fatigue and muscle ache. Unsolicited adverse events causally related to vaccination were reported in 18 subjects; none were of Grade 3 intensity. There were no serious adverse events. METHODS: This open-label, single-group, multi-center Phase II study enrolled 100 healthy subjects aged 20-64 years(stratification [1:1] by age: 20-40 years and 41-64 years) to receive 21 days apart, two doses of a monovalent, split-virion AS03(A)-adjuvanted H1N1 2009 pandemic vaccine (3.75 µg hemagglutinin [HA]). Blood samples collected before vaccination and 21 days after each dose were analyzed using hemagglutination inhibition (HI) assay. CONCLUSION: A single dose of AS 03A-adjuvanted, 3.75 µg HA H1N1 2009 pandemic influenza vaccine was highly immunogenic in Japanese adults with a clinically acceptable safety profile, thereby making it a potential candidate for mitigating A/H1N1-associated morbidity and mortality.

Reproducibility of blood pressure variation in older ambulatory and bedridden subjects.

OBJECTIVES: We investigated the influence of ambulation on the reproducibility of circadian blood pressure variation in older nursing home residents. DESIGN: Ambulatory blood pressure monitoring was performed twice in 37 older nursing home residents. SETTING: Nursing home in Japan. PARTICIPANTS: Subjects included 18 ambulatory nursing home residents who had no limitation on physical activity and 19 bedridden residents who did not participate in physical activity. MEASUREMENTS: Twenty-four-hour, daytime, and nighttime blood pressure levels and their variability. RESULTS: The 24-hour and daytime variability of systolic blood pressure (SBP) was significantly greater in ambulatory than in bedridden subjects, whereas nighttime variability was similar. Significant correlations in SBP averaged for the whole day, daytime, and nighttime were observed between the two examinations in ambulatory (r =.80-.83) and bedridden (r =.83-.91) subjects, but the variabilities of SBP for the whole day and during the daytime of the first measurement were correlated with those of the second measurement in bedridden (r =.67 and r =.47, respectively) but not in ambulatory (r =.39 and r =.28, respectively) subjects. Significant correlations were found between the nocturnal SBP changes at two occasions in both ambulatory (r =.50) and bedridden (r =.51) subjects, but the dipper versus nondipper profiles, defined as reduction in SBP of greater than 10% versus not, showed low reproducibility in ambulatory subjects; five ambulatory (28%) and one bedridden (5%) subjects showed divergent profiles between the two examinations. CONCLUSIONS: The reproducibility of blood pressure variation in nursing home residents is influenced by ambulation.

Characterization and long-term persistence of immune response following two doses of an AS03A-adjuvanted H1N1 influenza vaccine in healthy Japanese adults.

Background Long-term persistence of immune response and safety of two doses of an A/California/07/2009 H1N1 pandemic influenza vaccine adjuvanted with AS03 (an α-tocopherol oil-in-water emulsion-based Adjuvant System) administered 21 d apart was evaluated in Japanese adults [NCT00989612]. Methods One-hundred healthy subjects aged 20-64 y (stratified [1:1] into two age strata 20-40 y and 41-64 y) received 21 d apart, two doses of AS03-adjuvanted 3.75µg haemagglutinin (HA) H1N1 2009 vaccine. Immunogenicity data by haemagglutination inhibition (HI) assay six months after the first vaccine dose (Day 182) and microneutralization assay following each of the two vaccine doses (Days 21 and 42) and at Day 182 are reported here. Results Persistence of strong HI immune response was observed at Day 182 that met the US and European regulatory thresholds for pandemic influenza vaccines (seroprotection rate: 95%; seroconversion rate: 93%; geometric mean fold-rise: 20). The neutralizing antibody response against the A/Netherlands/602/2009 strain (antigenically similar to vaccine-strain) persisted for at least up to Day 182 (vaccine response rate: 76%; geometric mean titer: 114.4) and paralleled the HI immune response at all time points. No marked difference was observed in HI antibody persistence and neutralising antibody response between the two age strata. The vaccine had a clinically-acceptable safety profile. Conclusion Two priming doses of H1N1 2009 pandemic influenza vaccine induced an immune response persisting for at least six months after the first vaccine dose. This could be beneficial in evaluating the importance and effect of vaccination with this AS03-adjuvanted pandemic influenza vaccine.