Process for the preparation of a live non-virulent vaccine, Salmonella strain and vaccine containing this strain

摘要

Live vaccines are provided and methods for preparing the live vaccines for protection of a host from a pathogenic microorganism. The vaccines are prepared by introducing at least one modification in a gene involved in at least one, normally at least two, biosynthetic pathways, involving the production of products which are unlikely to be found in the disease susceptible host. The modification results in a gene change which cannot be repaired by a single step e.g. polynucleotide deletions and inversions. Where the aro gene suffers such a change, the resultant auxotrophic mutants require aromatic amino acids, p-aminobenzoic acid and 2, 3-dihydroxybenzoic acid or a highly concentrated source of absorbable iron. The auxotrophic mutations have substantially reduced or nonexistent virulence, while retaining the desired immunogenicity to initiate the immunogenic response. Various techniques can be employed for providing the desired change. Salmonella typhimurium strain SL1479 was deposited at the ATCC on September 7, 1982 and given ATGG Accession No. 39183; Salmonella dublin strain SL1438 was deposited on September 7, 1982 at the ATCC and given ATCC Accession No. 39184. Salmonella typhi strain 531Ty was deposited at the ATCC on November 21, 1984, and granted ATCC Accession No. 39926. This application is a continuation-in-part of U.S. Serial No. 675,381, filed November 27, 1984 which is a continuation-in-part of U.S. Serial No. 415,291, filed September 7, 1982 now U.S. Patent No. 4,550,081, issued October 29, 1985, which is a continuation-in-part of U.S. Serial No. 151,002, filed May 19, 1980, now abandoned, which disclosures are incorporated herein by reference.