Seropersistence of tick-borne encephalitis antibodies, safety and booster response to FSME-IMMUN 0.5 ml in adults aged 18-67 years.

A clinical study was carried out to evaluate the persistence of tick-borne encephalitis (TBE) antibodies 2 and 3 years after a primary vaccination series (three-dose regimen), and to assess the antibody response to a booster vaccination with FSME-IMMUN. Volunteers (N = 347, 18-67 years) who had received two doses of either FSME-IMMUN or Encepur adults and a third vaccination with FSME-IMMUN were enrolled. Seropositivity rates were assessed by ELISA and neutralization test (NT). After the primary series, seropositivity rates were 99.1% as determined by ELISA and 100% by NT, decreasing to 85% and 96.8% in the first two years and to 88.7% and 95.4% after 3 years. Following booster vaccination, 100% of subjects were seropositive. Age was the only variable with a significant influence on the probability of remaining TBE seropositive 2 or 3 years after the third vaccination. In subjects aged 18-50 years, the pre-booster seropositivity rate was higher (88.7% and 92.3% after 2 and 3 years, respectively) than in those aged 51-67 years (65.5% and 70.9% after 2 and 3 years, respectively). Adverse events after booster vaccination occurred with a low frequency and were predominantly mild. An annual TBE antibody decline rate of 0.58 (based on NT) was estimated to lead to antibody titer decrease from e.g., 260 to 45.6 after 3 years. To conclude, a booster vaccination with FSME-IMMUN, administered 3 years after primary vaccination, is well tolerated and induces a

A clinical trial of a whole-virus H5N1 vaccine derived from cell culture.

BACKGROUND: Widespread infections of avian species with avian influenza H5N1 virus and its limited spread to humans suggest that the virus has the potential to cause a human influenza pandemic. An urgent need exists for an H5N1 vaccine that is effective against divergent strains of H5N1 virus. METHODS: In a randomized, dose-escalation, phase 1 and 2 study involving six subgroups, we investigated the safety of an H5N1 whole-virus vaccine produced on Vero cell cultures and determined its ability to induce antibodies capable of neutralizing various H5N1 strains. In two visits 21 days apart, 275 volunteers between the ages of 18 and 45 years received two doses of vaccine that each contained 3.75 microg, 7.5 microg, 15 microg, or 30 microg of hemagglutinin antigen with alum adjuvant or 7.5 microg or 15 microg of hemagglutinin antigen without adjuvant. Serologic analysis was performed at baseline and on days 21 and 42. RESULTS: The vaccine induced a neutralizing immune response not only against the clade 1 (A/Vietnam/1203/2004) virus strain but also against the clade 2 and 3 strains. The use of adjuvants did not improve the antibody response. Maximum responses to the vaccine strain were obtained with formulations containing 7.5 microg and 15 microg of hemagglutinin antigen without adjuvant. Mild pain at the injection site (in 9 to 27% of subjects) and headache (in 6 to 31% of subjects) were the most common adverse events identified for all vaccine formulations. CONCLUSIONS: A two-dose vaccine regimen of either 7.5 microg or 15 microg of hemagglutinin antigen without adjuvant induced neutralizing antibodies against diverse H5N1 virus strains in a high percentage of subjects, suggesting that this may be a useful H5N1 vaccine. (ClinicalTrials.gov number, NCT00349141.)