Delving into the Latest Updates on E. coli vaccine (Intercell USA) with Synapse

Overview

Basic Info

Drug Type

Prophylactic vaccine

Synonyms

heat-labile enterotoxin of E. coli (LT)

Target-

Mechanism

Immunostimulants

Therapeutic Areas

Other Diseases

Active Indication-

Inactive Indication

Turista

Originator Organization

Intercell USA, Inc.

Active Organization-

Inactive Organization

Intercell USA, Inc.

Drug Highest PhasePendingPhase 2

First Approval Date-

Regulation-

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A polymer based dynamic combinatorial library (DCL) was generated through condensation between aldehyde functionalized linear poly(glycidol) (APG) and galactose containing acylhydrazide derivatives. Pentameric E. coli heat labile enterotoxin B subunit (LTB) was subsequently applied to the DCL as external stimulus, resulting in amplification of a specific acylhydrazone side chain that was further used for the synthesis of a multivalent LTB inhibitor. In the in vitro biological evaluation, this inhibitor exhibited strong inhibition properties as well as low cytotoxicity.

01 Dec 2018·BMC Infectious DiseasesQ3 · MEDICINE

Cross-reactive dengue virus-derived monoclonal antibodies to Zika virus envelope protein: Panacea or Pandora’s box?

Q3 · MEDICINE

ReviewOA

Author: Gunawardana, Shannon A ; Shaw, Robert H

BACKGROUNDDengue Virus (DENV) and Zika Virus (ZIKV) are closely related flaviviruses, circulating in overlapping geographical regions. The recent ZIKV epidemic has been linked to an explosion in reports of microcephaly and neurological defects. It is conceivable that our knowledge of DENV might potentiate the development of a ZIKV vaccine due to the close phylogenetic relationship between these flaviviruses and cross-reactive antibodies, principally to the envelope protein (E protein). Alternatively, cross-reactive antibodies that are generated following vaccination or infection, might become damaging during subsequent infections.MAIN BODYThe aims of this review are to collate and analyse data from a recent series of DENV-derived monoclonal antibody (mAb) panels from different research groups. These panels measured DENV-mAb activity against ZIKV in terms of antibody-dependent enhancement (ADE) and neutralisation. Methodology used across groups was compared and critiqued. Furthermore, the specific antibody targets on E protein were considered and their therapeutic potential evaluated. Shortcomings of hmAb panels suggest ADE may be over-estimated and neutralisation underestimated, as compared to clinical situations. It remains unknown whether preference of enhancement or neutralisation by antibodies to ZIKV E protein is dictated by quantitative aspects of antibody titre or epitope specific variation. Additionally, little is known about how duration between flavivirus reinfections affect secondary antibody response.CONCLUSIONThis review concludes that our current knowledge of cross-reactive antibodies to E protein is inadequate to anticipate the outcome of deploying an E protein based vaccine to regions co-infected by DENV and ZIKV.

01 Mar 2017·VaccineQ3 · MEDICINE

Skin vaccination via fractional infrared laser ablation - Optimization of laser-parameters and adjuvantation

Q3 · MEDICINE

Article

Author: Strobl, Anna ; Thalhamer, Josef ; Steiner, Martin ; Thalhamer, Theresa ; Scheiblhofer, Sandra ; Hoepflinger, Veronika ; Weiss, Richard

BACKGROUNDMethods to deliver an antigen into the skin in a painless, defined, and reproducible manner are essential for transcutaneous immunization (TCI). Here, we employed an ablative fractional infrared laser (P.L.E.A.S.E. Professional) to introduce clinically relevant vaccines into the skin. To elicit the highest possible antibody titers with this system, we optimized different laser parameters, such as fluence and pore number per area, and tested various adjuvants.METHODSBALB/c mice were immunized with Hepatitis B surface antigen (HBsAg) by laser-microporation. Adjuvants used were alum, CRM₁₉₇, monophosphoryl lipid A, heat-labile enterotoxin subunit B of E. coli (LT-B), and CpG ODN1826. The influence of different fluences (2.1 to 16.8J/cm²) and pore densities (5-15%) was investigated. Furthermore, immunogenicity of HBsAg and the commercially available conjugate vaccines ActHIB® and Menveo® applied via TCI was compared to standard i.m. injection. Antigen-specific antibody titers were assessed by luminometric ELISA.RESULTSAntibody titers against HBsAg were dependent on pore depth and peaked at a fluence of 8.4J/cm². Immunogenicity was independent of pore density. Adjuvantation with alum significantly reduced antibody titers after TCI, whereas other adjuvants only induced marginal changes in total IgG titers. LT-B and CpG shifted the polarization of the immune response as indicated by decreased IgG1/IgG2a ratios. HBsAg/LT-B applied via TCI induced similar antibody titers compared to i.m. injection of HBsAg/alum. In contrast to i.m. injection, we observed a dose response from 5 to 20μg after TCI. Both, ActHIB® and Menveo® induced high antibody titers after TCI, which were comparable to i.m. injection.CONCLUSIONSAlum, the most commonly used adjuvant, is contraindicated for transcutaneous vaccination via laser-generated micropores. TCI with optimized laser parameters induces high antibody titers, which cannot be significantly increased by the tested adjuvants. Commercially available vaccines formulated without alum have the potential for successful TCI via laser-generated micropores, without the need for reformulation.

100 Deals associated with E. coli vaccine (Intercell USA)

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Turista	Phase 2	US	Intercell USA, Inc.	01 Nov 2007

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT00751777 (CTgov)	Phase 2	Turista	120	heat-labile enterotoxin of E. coli (LT) (Group 1: 37.5 µg LT Patch)	orpvffzsju(dsophizueb) = tjejnbsuef zcvoiezdkl (dasjqymotk, jjsqqkvfkh - vqxiahwpwe) View more	-	21 Apr 2014
				Placebo (Group 2: 0 µg LT Patch (Placebo))	orpvffzsju(dsophizueb) = jetgqipotg zcvoiezdkl (dasjqymotk, kgkyohkoiz - toliamhbyq) View more