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eVLP Platform

Enveloped Virus-like Particle Vaccines

eVLP Platform Overview

VBI’s eVLP Platform allows for the design of enveloped (“e”) virus-like particle (“VLP”) vaccines. eVLPs are an innovative new class of synthetic vaccines that are designed to closely mimic the structure of viruses.

Because of their structural similarity to viruses found in nature, vaccination with a target protein expressed in an eVLP is capable of imparting greater immunity than vaccination with the same recombinant target protein alone.1 VBI is focused first on applying its eVLP technology to develop a vaccine to prevent cytomegalovirus (“CMV”) infection.

Platform Highlights
  • “Third-generation” virus-like particle vaccines closely mimic the structure of target viruses.
  • Potential preventative and therapeutic vaccine applications.
  • Lead program is a vaccine to prevent cytomegalovirus (“CMV”) infection with strong preclinical proof of concept.2
  • Exploring additional undisclosed eVLP candidates for development.
  • Strong intellectual property estate.

Dr. David Anderson, VBI’s Chief Scientific Officer, discusses VBI’s unique approach to vaccine development.

Virus-like Particle Vaccines

About Virus-like Particles

Virus-like particles (“VLPs”) are protein structures designed to mimic the organization and conformation of viruses as they occur in nature but without the viral genome, potentially yielding safer and more potent vaccine candidates.

Unlike first-generation and second-generation VLP approaches, which have yielded successful vaccines but can mean limited rational and flexible design potential, VBI’s eVLP Platform provides a stable foundation that mimics enveloped viruses and is suitable for a wide array of vaccine candidates.3

eVLP Advantages
  • Highly Immunogenic: Immune responses comparable to or better than natural infection by closely mimicking structure of target virus.4
  • Customizable: Ability to rationally design a vaccine by including different antigens and controlling their relative expression.
  • Safe: Unlike live-attenuated vaccines, VLPs cannot revert back to an infectious state.
  • Commercially Viable: Manufactured and purified using scalable methods; demonstrated high yields and purity.5
eVLP Vaccine Components and Design

The Evolution of Virus-like Particle Vaccines

First-Generation Second-Generation Third-Generation (eVLP Platform)
Design Antigens are produced and self-assemble. Antigens of interest are covalently attached to the surface of a backbone protein. Common protein backbone and lipid membrane in which the antigen of interest can be expressed.
Advantage(s) Simple structures and repetitive pattern of antigenic epitopes. Can be applied to multiple different target antigens; VLP structure is not limited to the properties of the antigen. Enables more natural presentation of target antigen within a membrane that more closely mimics a virus; can express multiple target antigens in a single VLP.
Limitation(s) Only a very limited number of antigens spontaneously form orderly VLP structures; cannot be applied to all enveloped viruses. Antigen of interest is artificially bound to the structural protein and not represented in a natural configuration. Additional process knowledge needed to meet FDA/EMA purification standards.

Customizable Design to Tailor the Immune Response

eVLPs are highly customizable, which allows VBI to rationally design preventative or therapeutic vaccine candidates by controlling the expression of both surface and internal target proteins of interest.

To learn more about partnership opportunities, contact us.

Monovalent
Bivalent – Multiple Surface Proteins
Bivalent – Internal Protein
Trivalent – Internal Protein

Manufacturing

VBI has demonstrated the ability to manufacture eVLPs with yields and purity that are expected to be suitable for vaccine production at a commercial scale.6

Process Highlights
  • eVLPs are produced after transient transfection of cells with plasmids encoding the murine leukemia virus (“MLV”) Gag and target surface or internal proteins of interest.
  • MLV Gag expression induces “budding” of particles from membrane of transfected cells; the target protein of interest is incorporated into the outer envelope during the budding process.
  • eVLPs are purified using a process designed to yield material with acceptable residual host cell impurities.
  • Batch consistency is demonstrated using an in vivo potency release assay.

Electron microscopy images of VBI’s eVLP-derived CMV Vaccine Candidate, captured at The Scripps Institute.

References

  1. Kirchmeier M, Fluckiger AC, Soare C, et al. Enveloped virus-like particle expression of human cytomegalovirus glycoprotein B antigen induces antibodies with potent and broad neutralizing activity. Clin Vaccine Immunol. 2014;21(2):174-80.
  2. VBI Studies: 15BC04, 15BC19, 15BC39
  3. VBI studies: 15BC04, 15BC19 (CMV); Garrone, P (2011) Sci Transl Med 3, 94ra71 (HCV); Szecsi, J (2006) Virol J 3, 70 (Flu)
  4. VBI Studies: 15BC04, 15BC19
  5. VBI Studies: 15CH19, 15CH38
  6. VBI 2015 MVADS Conference Presentation

Pipeline of eVLP-Derived Vaccine Candidates

Discovery

Preclinical

Phase I

CMV

Cytomegalovirus
Phase I

Phase I

85%

GBM

Glioblastoma multiforme
Preclinical

Preclinical

50%

MB

Medulloblastoma
Preclinical

Preclinical

45%

Zika virus
Discovery

Discovery

30%

RSV

Respiratory syncytial virus
Discovery

Discovery

30%

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