Clinical and immune response to undiluted and diluted smallpox vaccine.

QUESTION UNDER STUDY To assess clinical reactions, immune responses and adverse events to undiluted, three- and sixfold diluted Lister strain vaccine stockpiled in Switzerland. METHODS A prospective, triple-blinded, randomised, parallel group clinical trial was performed. RESULTS From 2001 to 2007 104 persons with an indication for vaccinia vaccination were recruited. They had a median age of 33 years (range 18-65), 56 (53.8%) were re-vaccinees and 48 (46.2%) primary vaccinees. There was no statistically significant variation in the proportion of revaccinees between diluted and undiluted vaccine groups (75% vs 51%, p = 0.118). With an overall clinical take rate (major reaction) of 97.1% the majority of the vaccinia-naïve participants exhibited an at least fourfold increase of neutralising antibody titres (32/38, 84.2%) post-vaccination. Interestingly this proportion was lower among re-vaccinees (29/46, 63.0%, p = 0.048). No significant difference was observed in the take rate or at least fourfold seroconversion rate between the threefold and sixfold diluted vaccine doses. Adverse events were reported by 98 (94.2%) participants, not accounting for itching at the vaccination site. CONCLUSION Subjects requiring immunisation were successfully (re-) vaccinated with undiluted as well as with three- or sixfold diluted vaccinia vaccine. Our findings complement previous studies with respect to the clinical take rate and immune response. The rate of adverse events was substantial but not unexpected and no severe adverse events occurred. In conclusion, the existing smallpox vaccine stockpile might be expanded by administering three- or sixfold diluted vaccine doses combined with a careful pre-vaccination screening and extensive instructions to vaccinees.