Construction and preclinical evaluation of recombinant Peru-15 expressing high levels of the cholera toxin B subunit as a vaccine against enterotoxigenic Escherichia coli.

Construction and preclinical evaluation of recombinant Peru-15 expressing high levels of the cholera toxin B subunit as a vaccine against enterotoxigenic Escherichia coli. Research Abstract Details 

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Construction and preclinical evaluation of recombinant Peru-15 expressing high levels of the cholera toxin B subunit as a vaccine against enterotoxigenic Escherichia coli. Abstract Text:

Kenneth L Roland,Cheryl Cloninger,Sims K Kochi,Lawrence J Thomas,Steven A Tinge,Craig Rouskey,Kevin P Killeen,Kenneth L Roland,Cheryl Cloninger,Sims K Kochi,Lawrence J Thomas,Steven A Tinge,Craig Rouskey,Kevin P Killeen,Kenneth L Roland,Cheryl Cloninger,Sims K Kochi,Lawrence J Thomas,Steven A Tinge,Craig Rouskey,Kevin P Killeen,

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.

Construction and preclinical evaluation of recombinant Peru-15 expressing high levels of the cholera toxin B subunit as a vaccine against enterotoxigenic Escherichia coli. Publishing Authors By Initials

KL Roland,C Cloninger,SK Kochi,LJ Thomas,SA Tinge,C Rouskey,KP Killeen,KL Roland,C Cloninger,SK Kochi,LJ Thomas,SA Tinge,C Rouskey,KP Killeen,KL Roland,C Cloninger,SK Kochi,LJ Thomas,SA Tinge,C Rouskey,KP Killeen,

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Construction and preclinical evaluation of recombinant Peru-15 expressing high levels of the cholera toxin B subunit as a vaccine against enterotoxigenic Escherichia coli. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Vaccine

VOLUME: 25

Page Numbers: 8574-84

Journal Abbreviation: Vaccine

ISSN: 0264-410X

DAY: 26

MONTH: 10

YEAR: 2007

Construction and preclinical evaluation of recombinant Peru-15 expressing high levels of the cholera toxin B subunit as a vaccine against enterotoxigenic Escherichia coli. Information

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LANGUAGE: eng

NlmUniqueID: 8406899

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Grant and Affiliation Information for Construction and preclinical evaluation of recombinant Peru-15 expressing high levels of the cholera toxin B subunit as a vaccine against enterotoxigenic Escherichia coli.

AFFILIATION: AVANT Immunotherapeutics, Inc. 119 Fourth Avenue, Needham, MA 02494, United States.

Country: Netherlands

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MEDLINETA: Vaccine

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