Entwicklung einer numerisch-additiven Kombinationsvaccine gegen tetanus und Pocken: Development of a combination vaccine against tetanus and smallpox

Abstract

Mandatory vaccination against smallpox was abolished on the account of smallpoxeradication proclaimed by the WHO and the postvaccinal complications detected after smallpox vaccination. At the same time vaccine banks with the vaccinia virus strain “Elstree” were organized. Should mass vaccinations with this vaccinia virus strain be carried out in a case of emergency, severe postvaccinal diseases and complications can arise in overaged and immunosuppressed vaccinees after primovaccination. Therefore attenuated vaccinia virus strains should be used for vaccine banks, which cannot be activated, or increase in virulence in impaired vaccinees after primovaccination. For these individuals the vaccinia virus strain “MVA”, among other attenuated vaccinia strains, is recommended. The MVA virus strain can be applied parenterally without complications. From the scientific and field-relevant point of view it was tried to combine the vaccinia virus strain “MVA” with tetanus toxoid and to develop a combination vaccine “tetanus-smallpox”. In immunization experiments using mice, piglets and monkeys, safety and efficacy of the vaccine were investigated. Efficacy was demonstrated by means of postvaccinal antibody determination and by the mouse protection test. Tetanus antitoxin was measured by ELISA and indirect hemagglutination test, antibody levels to vaccinia virus were investigated employing the neutralization test and hemagglutination inhibition test. No significant differences in potency could be demonstrated between the combination vaccine and the corresponding monovalent vaccines in mice, piglets and monkeys. The combination vaccine consisted of 12 Lf tetanus toxoid and 10 8,25 TCID 50 vaccinia virus “MVA” preserved with gelatine and glucosamine. The double intramuscular immunization of monkeys stimulated average tetanus antitoxin titers of 1:310 and average vaccinia virus titers of 1:195 2 weeks p. revacc. Similar results were obtained in mice and piglets. Side reactions were not observed in mice and piglets. Except for occasional local reactions of short duration at the injection site of the monkeys, similarly no adverse reactions were observed after intramuscular vaccination with the combination vaccine.