Immunization against Anthrax with Aromatic-Dependent (Aro-) Mutants of Bacillus anthracis and with Recombinant Strains of Bacillus subtilis Producing Anthrax Protective Antigen.

摘要

The safety and efficacy of five prototype, live anthrax vaccines were studied in Hartly guinea pigs and CBA/J and A/J mice. Two of the strains, Bacillus anthracis FD111 and FD112, are Aro-mutants derived by transposon mutagenesis UM23-1. B. subtilis strains PA1 and PA2 contain a recombinant plasmid, pPA101 or pPA102 respectively, that carries the gene from B. anthracis encoding protective antigen (PA). B. subtilis DB-104 transformed with pPA101. All five strains were less virulent in guinea pigs and A/J and CBA/J mice than the toxinogenic nonencapsulated B. anthracis veterinary vaccine Sterne strain. A/J and CBA/J inbred mice represent mouse strains that are innately susceptible and resistant, respectively, to the Sterne strain. These differences in susceptibility are due to differences in ability to produce complement component 5. In guinea pigs immunization with PA1 or PA2 vegetative cells or PA7 spores protected 95% or greater from an intramuscular spore challenge of the virulent, 'vaccine-resistant' B. anthracis Ames strain. Strain PA2 vegetative cells and strain PA7 spores were as effective as the Sterne strain in Sterne-resistant CBA/J mice. Immunization with FD111 or FS112 vegetative cells fully protected guinea pigs from challenge. Immunization with FD111 cells protected up to 100% of CBA/J mice and up to 70% of A/J mice Keywords: DNA; Clones. (AW)