PMID- 2101489
OWN - NLM
STAT- MEDLINE
DCOM- 19910909
LR  - 20190918
IS  - 0923-2508 (Print)
IS  - 0923-2508 (Linking)
VI  - 141
IP  - 7-8
DP  - 1990 Sep-Oct
TI  - Vaccines against enterotoxigenic bacterial pathogens based on hybrid Salmonella 
      that express heterologous antigens.
PG  - 981-93
AB  - In this report, we examine two aspects in the development of a vaccine against 
      enterotoxigenic bacterial pathogens based on hybrid Salmonella that express 
      heterologous antigens. First, we describe the construction of a non-toxic fusion 
      peptide for immunization against Escherichia coli that produce heat-labile (LT) 
      and heat-stable (ST) enterotoxins. For that construction, the 5' terminus of the 
      gene coding for ST was fused to the 3' terminus of the gene coding for the 
      binding subunit of LT(LT-B). The ST gene was constructed synthetically with 
      appropriate restriction sites to permit in-frame, downstream insertion. Maximum 
      expression of ST antigenicity was obtained when a seven-amino-acid 
      proline-containing linker was included between the LT-B and ST moieties. The 
      purified LT-B/ST fusion peptide consisted of a single polypeptide chain with an 
      apparent molecular weight of 18,000. The LT-B/ST fusion peptide was non-toxic and 
      immunologic determinants of both LT and ST were recognized by antibodies directed 
      against the native toxins. Animals immunized with either crude or purified 
      preparations containing the hybrid molecule produced antibodies that were able to 
      recognize native toxin in vitro. Significantly, these antibodies were able to 
      neutralize the biological activity of native ST. The second aspect reported here 
      examines a mechanism for stabilizing expression of heterologous antigens in 
      attenuated Salmonella mutants by integration of the heterologous gene (LT-B) into 
      the chromosome of the carrier. A comparative in vitro study of the levels of 
      expression of LT-B between the cointegrate strain and an isogenic strain carrying 
      the LT-B gene on a multicopy plasmid demonstrated that the initial levels of 
      expression of both strains is similar, that the plasmid-carrying strain loses the 
      ability to express the heterologous antigen very quickly and that the cointegrate 
      continues to maintain and express the antigen without the requirement for a 
      stabilizing antibiotic.
FAU - Clements, J D
AU  - Clements JD
AD  - Department of Microbiology and Immunology, Tulane University School of Medicine, 
      New Orleans, LA 70112.
FAU - Cardenas, L
AU  - Cardenas L
LA  - eng
PT  - Journal Article
PL  - France
TA  - Res Microbiol
JT  - Research in microbiology
JID - 8907468
RN  - 0 (Antigens, Bacterial)
RN  - 0 (Bacterial Vaccines)
RN  - 0 (DNA, Bacterial)
RN  - 0 (Enterotoxins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Vaccines, Synthetic)
SB  - IM
MH  - Animals
MH  - *Antigens, Bacterial/genetics
MH  - Bacterial Vaccines/genetics/*isolation & purification
MH  - Base Sequence
MH  - Cloning, Molecular
MH  - DNA, Bacterial/genetics
MH  - Enterotoxins/genetics
MH  - Escherichia coli/genetics/immunology
MH  - Female
MH  - Mice
MH  - Molecular Sequence Data
MH  - Recombinant Fusion Proteins/genetics/immunology
MH  - Salmonella typhimurium/genetics/*immunology
MH  - Vaccines, Synthetic/genetics/isolation & purification
EDAT- 1990/09/01 00:00
MHDA- 1990/09/01 00:01
CRDT- 1990/09/01 00:00
PHST- 1990/09/01 00:00 [pubmed]
PHST- 1990/09/01 00:01 [medline]
PHST- 1990/09/01 00:00 [entrez]
AID - 0923-2508(90)90138-G [pii]
AID - 10.1016/0923-2508(90)90138-g [doi]
PST - ppublish
SO  - Res Microbiol. 1990 Sep-Oct;141(7-8):981-93. doi: 10.1016/0923-2508(90)90138-g.