PMID- 18045752
OWN - NLM
STAT- MEDLINE
DCOM- 20080331
LR  - 20220321
IS  - 0264-410X (Print)
IS  - 0264-410X (Linking)
VI  - 25
IP  - 51
DP  - 2007 Dec 12
TI  - Construction and preclinical evaluation of recombinant Peru-15 expressing high 
      levels of the cholera toxin B subunit as a vaccine against enterotoxigenic 
      Escherichia coli.
PG  - 8574-84
AB  - Enterotoxigenic Escherichia coli (ETEC) is the leading cause of traveler's 
      diarrhea. The heat-labile (LT) and heat-stable (ST) toxins mediate ETEC induced 
      diarrhea. ETEC strains may express LT, ST, or both LT and ST, with LT-expressing 
      strains accounting for approximately 50-60% of ETEC-related traveler's diarrhea. 
      Cholera toxin (CT) is >80% homologous to LT and vaccination with CT-B subunit 
      (CT-B) -based vaccines elicit a protective immune response against LT-producing 
      ETEC strains. Peru-15 is an oral, single-dose, live-attenuated cholera vaccine 
      candidate that has been investigated in several clinical trials (n>400 subjects) 
      and was proven well tolerated, immunogenic, and efficacious. Peru-15 was 
      genetically engineered to express and secrete high levels of CT-B by cloning ctxB 
      onto a glnA balanced-lethal plasmid under the transcriptional control of a strong 
      constitutive promoter, resulting in Peru-15pCTB. In vitro characterization 
      demonstrated that Peru-15pCTB secreted approximately 30-fold more CT-B than 
      Peru-15 and CT-B was stably produced after 40 generations of growth and 
      throughout simulated Seed Bank and FDP (Final Drug Product) production 
      conditions. In preclinical studies, the geometric mean anti-CT-B IgG titer in the 
      sera of mice inoculated intranasally with two doses of Peru-15pCTB was >32-fold 
      higher than in mice inoculated with Peru-15. Similarly, rabbits orally inoculated 
      with a single dose of Peru-15pCTB developed titers that were approximately 
      30-fold higher than rabbits inoculated with a single dose of Peru-15. Sera from 
      Peru-15pCTB vaccinated mice and rabbits neutralized LT toxicity in an in vitro 
      assay. Peru-15pCTB has several promising characteristics of an oral, single-dose, 
      bivalent cholera/ETEC vaccine and is advancing towards a Phase 1 clinical trial.
FAU - Roland, Kenneth L
AU  - Roland KL
AD  - AVANT Immunotherapeutics, Inc. 119 Fourth Avenue, Needham, MA 02494, United 
      States.
FAU - Cloninger, Cheryl
AU  - Cloninger C
FAU - Kochi, Sims K
AU  - Kochi SK
FAU - Thomas, Lawrence J
AU  - Thomas LJ
FAU - Tinge, Steven A
AU  - Tinge SA
FAU - Rouskey, Craig
AU  - Rouskey C
FAU - Killeen, Kevin P
AU  - Killeen KP
LA  - eng
PT  - Journal Article
DEP - 20071026
PL  - Netherlands
TA  - Vaccine
JT  - Vaccine
JID - 8406899
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (Antibodies, Bacterial)
RN  - 0 (Cholera Vaccines)
RN  - 0 (Culture Media)
RN  - 0 (Immunoglobulin G)
RN  - 0 (Vaccines, Synthetic)
RN  - 9012-63-9 (Cholera Toxin)
SB  - IM
MH  - Adjuvants, Immunologic/*genetics
MH  - Administration, Intranasal
MH  - Animals
MH  - Antibodies, Bacterial/analysis/biosynthesis
MH  - Antibody Specificity
MH  - Blotting, Western
MH  - Cholera Toxin/*genetics/*immunology
MH  - Cholera Vaccines/administration & dosage/*genetics/*immunology
MH  - Culture Media
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Enterotoxigenic Escherichia coli/*immunology
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Escherichia coli Infections/*immunology
MH  - Immunoglobulin G/analysis/biosynthesis/immunology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Neutralization Tests
MH  - Plasmids/genetics
MH  - Rabbits
MH  - Vaccines, Synthetic/genetics/immunology
MH  - Vibrio cholerae/immunology
EDAT- 2007/11/30 09:00
MHDA- 2008/04/01 09:00
CRDT- 2007/11/30 09:00
PHST- 2007/08/22 00:00 [received]
PHST- 2007/09/18 00:00 [revised]
PHST- 2007/09/25 00:00 [accepted]
PHST- 2007/11/30 09:00 [pubmed]
PHST- 2008/04/01 09:00 [medline]
PHST- 2007/11/30 09:00 [entrez]
AID - S0264-410X(07)01112-7 [pii]
AID - 10.1016/j.vaccine.2007.09.074 [doi]
PST - ppublish
SO  - Vaccine. 2007 Dec 12;25(51):8574-84. doi: 10.1016/j.vaccine.2007.09.074. Epub 
      2007 Oct 26.