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nCage Therapeutics
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Technology

Synthetic VLP Vaccines

nCage's cage mimics the structure of a virus — the shape the immune system is built to recognise — without any of the genetic material that makes a virus infectious.

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nCage's science

TRAP-cages act as synthetic virus-like particle vaccines, driving a greater immune response and lasting protection for patients.

Comparison

Three ways to show an antigen

A virus: repeating surface antigens around a genetic core.
Fig. 01A virus: repeating surface antigens around a genetic core.

Reference point

Typical virus

  • Displays antigens across a repeating protein shell — the pattern the immune system responds to most strongly.
  • Carries genetic material, which is what makes it infectious.
A synthetic VLP: viral exterior, no genetic material.
Fig. 02A synthetic VLP: viral exterior, no genetic material.

Current state of the art

Synthetic VLP

  • Variants have been tested by nCage and its competition.
  • Resembles the exterior of a virus and can be used as a vaccine.
  • Antigens mounted only externally.
  • Very strong immune response, already proven in clinical trials.
A TRAP-cage: antigens mounted inside and out.
Fig. 03A TRAP-cage: antigens mounted inside and out.

nCage

TRAP-cage

  • A specific synthetic VLP developed by nCage.
  • Programmable opening and closing supports improved vaccine designs.
  • Internally mounted antigens create the chance for an even stronger response.
  • A virus-like structure with scope for greater efficacy than current approaches.

01The virus-like structure is easily recognised by the body, and delivers a large number of antigens close together — which increases the immune response.

02Unlike viruses, synthetic VLPs are non-infectious, because they contain no genetic material.

Manufacture

How nCage makes a TRAP-cage

Three steps, in order. Each one adds something the previous step made possible.

  1. 01

    The scaffold

    TRAP proteins are connected by gold links, which give the cage its stability.

    TRAP protein scaffold
  2. 02

    Add-ons

    Hooks and antigens are then attached to the cage.

    Hook component
    Second hook component
    Antigen component
    Second antigen component
  3. 03

    Synthetic VLP

    The finished particle carries antigens on both the interior and the exterior of the cage.

    Completed TRAP-cage

Vaccination leading to a strong immune response

The case for VLPs

VLP vaccines are the most effective on the market

Antigen presented on a protein cage engages multiple B cell receptors, producing higher and longer-lasting immunity than soluble protein.
Fig. 04Antigen presented on a protein cage engages multiple B cell receptors, producing higher and longer-lasting immunity than soluble protein.
01

Naturally occurring VLPs significantly increase and extend immunity

Compared with soluble protein vaccines, protein cages displaying antigen engage multiple receptors of B cells in germinal centres. Those B cells retrieve and process larger amounts of antigen and interact more strongly with follicular T helper cells.

The result is higher levels and longer duration of immunity.

An enhanced response matters most in elderly populations, where immunosenescence reduces responsiveness to conventional vaccines.

02

But they exist for only two viruses

Naturally occurring VLPs have been developed into successful vaccines twice: Cervarix against human papillomavirus, and Recombivax HB against hepatitis B.

03

Synthetic VLPs remove that limit

Synthetic VLPs work the same way as naturally occurring ones, but can be built for any virus.

Possible combination of antigens. Longer antibody persistence. Maximised antigen density. Easy manufacturing.

Expected advantages

What a synthetic VLP vaccine offers over other vaccine types

  • Fewer side effects
  • Easier manufacturing
  • Stronger immune response
  • Possible vaccine combination
  • Higher durability
  • Broader coverage of variants

Synthetic VLP vaccines have the potential to dominate future vaccine manufacturing.

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Peer-reviewed

See the seminal Nature article that provides foundational information on nCage Therapeutics' technology

An ultra-stable gold-coordinated protein cage displaying reversible assembly

Nature · Vol 569 · 16 May 2019

An ultra-stable gold-coordinated protein cage displaying reversible assembly

Malay, A. D., Miyazaki, N., Biela, A., Chakraborti, S., Majsterkiewicz, K., Stupka, I., Kaplan, C. S., Kowalczyk, A., Piette, B. M. A. G., Hochberg, G. K. A., Wu, D., Wrobel, T. P., Fineberg, A., Kushwah, M. S., Kelemen, M., Vavpetič, P., Pelicon, P., Kukura, P., Benesch, J. L. P., Iwasaki, K. & Heddle, J. G.