Rivabazumab Overview

Introduction Mechanisms Clinical Projects What We Provide

Introduction of Rivabazumab

Rivabazumab is a recombinant antibody specifically designed to target the pcrV protein of Pseudomonas aeruginosa (P. aeruginosa ). This antibody represents a promising approach in combating P. aeruginosa infections, particularly in increasing antibiotic resistance. Initially developed by KaloBios Pharmaceuticals, rivabazumab pegol (KB001) is a pegylated version of the antibody. In 2013, the U.S. Food and Drug Administration granted orphan drug designation to KB001 for treating cystic fibrosis (CF) patients with Pseudomonas aeruginosa infections.

Biological and Chemical Properties of Type III Secretion Protein PcrV

Protein Structure

Figure 1. The Structural Features of Type III Secretion Protein PcrVFigure 1. The Structure of Type III Secretion Protein PcrV (UniProt)1,2

The Mechanism of Rivabazumab Action

Rivabazumab exerts its therapeutic effects by specifically binding to the pcrV protein of P. aeruginosa, thereby inhibiting its function within the Type III secretion system (T3SS). The T3SS is a multi-protein complex employed by numerous pathogenic Gram-negative bacteria, including Salmonella, Shigella, Yersinia, Pseudomonas, Vibrio, and Escherichia. This system is pivotal for bacterial virulence, facilitating the evasion of host immune responses and promoting bacterial survival and proliferation. The pcrV protein is a crucial component of P. aeruginosa's T3SS. Structurally, it forms a needle-like appendage that regulates the translocation of effector proteins into the host cytoplasm. In normal conditions, pcrV functions as part of the T3SS to manipulate host cellular processes, facilitating bacterial colonization and infection. However, in pathological scenarios, the overexpression or hyperactivation of the T3SS can enhance P. aeruginosa virulence, leading to severe tissue damage, inflammation, and compromised host defenses. This contributes to chronic infections, particularly in immunocompromised individuals and those with underlying conditions like cystic fibrosis or chronic wounds.

Upon administration, rivabazumab targets the infected tissue and binds specifically to the pcrV protein with its antigen-binding site, forming a stable antigen-antibody complex. This complex effectively blocks the T3SS apparatus and prevents the translocation of effector proteins into host cells, thus neutralizing bacterial virulence mechanisms. As a result, P. aeruginosa's virulence is reduced, leading to enhanced bacterial clearance by the host immune system. Additionally, the compromised infection machinery limits bacterial growth and dissemination, contributing to a favorable therapeutic outcome.

Figure 2. Rivabazumab Targets the pcrV protein and Blocks T3SS, Preventing the Translocation of Effector ProteinsFigure 2. The Mechanism of Rivabazumab Action3,4

Clinical Projects of Rivabazumab pegol (KB001) *

NCT ID Study Title Study Status Conditions Sponsor Start Date
NCT01695343 Study to Evaluate the Effect of KB001-A on Time-to-Need for Antibiotic Treatment COMPLETED Cystic Fibrosis Humanigen, Inc. 2012-12
NCT00691587 Pilot Trial of KB001 in Mechanically-Ventilated Patients Colonized with Pseudomonas Aeruginosa COMPLETED Pseudomonas Aeruginosa
Ventilator Associated Pneumonia
Humanigen, Inc. 2008-04
NCT00638365 Dose Escalation Study of KB001 in Cystic Fibrosis Patients Infected With Pseudomonas Aeruginosa COMPLETED Cystic Fibrosis Humanigen, Inc. 2008-03

* The table is excerpted from the following website: https://clinicaltrials.gov/search?cond=KB001-A

What We Provide

Rivabazumab

Anti-Pseudomonas Aeruginosa pcrV Recombinant Antibody Fab Fragment (Rivabazumab)

Creative Biolabs offers high-quality rivabazumab, specifically designed for use in Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Immunofluorescence, Immunoprecipitation, Flow Cytometry and Functional Studies. This product is designed for lab research use only, and is not suitable for diagnostic, therapeutic, or any in vivo human use.

Specification
  • Immunogen
  • The details of the immunogen for this antibody are not available.
  • Host Species
  • Human
  • Derivation
  • Humanized
  • Type
  • Fab' G1-κ
  • Specificity
  • Pseudomonas aeruginosa type III secretion system (TTSS)PcrV protein
  • Species Reactivity
  • Pseudomonas aeruginosa
  • Applications
  • Used for immunoassay techniques such as: Enzyme-Linked Immunosorbent Assay; Immunohistochemistry; Immunofluorescence; Immunoprecipitation; Flow Cytometry; Functional Studies
  • Conjugate
  • Unconjugated
  • CAS
  • 1613506-32-3
  • Generic Name
  • Rivabazumab
  • UNII
  • T3V24FDA87
  • Related Disease
  • Pseudomonas aeruginosa infections

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References
  1. Uniprot Database (https://www.uniprot.org/uniprotkb/G3XD49/entry#function)
  2. The image was retrieved from UniProt Database and used under [CC BY 4.0]. It was not modified and the title was "The Structure of Type III Secretion Protein PcrV".
  3. Sundin, Charlotta et al. "Identification of Small Molecules Blocking the Pseudomonas aeruginosa type III Secretion System Protein PcrV." Biomolecules vol. 11,1 55. 4 Jan. 2021.
  4. Images retrieved from Figure 1 " Identification of Small Molecules Blocking the Pseudomonas aeruginosa type III Secretion System Protein PcrV." Sundin, Charlotta, 2021, used under [CC BY 4.0] (https://creativecommons.org/licenses/by/4.0/). The image was modified by adding the text "Rivabazumab" and the title was changed to " The Mechanism of Rivabazumab Action".

For research use only. Not intended for any clinical use.

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