Recombinant NDV Expressing Lassa Antigens for BSL-4 Vaccine Development

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Solution Overview

Problem

There is a need for effective vaccines and treatments against Lassa fever, as the current situation lacks approved vaccines and specific antiviral treatments, and the virus is classified under the highest biosafety level (BSL-4), hindering diagnostics and vaccine development.

Innovation Solution

Development of recombinant Newcastle disease virus (NDV) expressing Lassa virus glycoprotein or nucleoprotein, or a chimeric protein comprising the ectodomain of Lassa virus glycoprotein and the transmembrane and cytoplasmic domains of NDV F protein, along with immunogenic compositions and methods for immunization.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If Lassa virus is classified under BSL-4, then biosafety is improved, but vaccine development and diagnostics are hindered

Engineering Contradiction:

ImprovebiosafetyVSAvoidvaccine development

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent uses Newcastle disease virus (NDV) as an intermediary vector to deliver Lassa virus antigens. The NDV vector system allows vaccine development without requiring direct handling of BSL-4 Lassa virus, as the recombinant NDV can be safely manipulated in lower biosafety laboratories while still expressing the immunogenic Lassa virus glycoprotein or nucleoprotein

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent creates recombinant NDV that copies only the essential immunogenic components (antigens) of the Lassa virus rather than using the complete BSL-4 virus. This copying approach preserves the ability to induce immune responses while eliminating the need to work with the hazardous full-length Lassa virus

Inventive Principle:

Principle #26Copying

2Reliability

If no approved vaccine exists for Lassa fever, then treatment options are limited, but development of new vaccines is necessary

Engineering Contradiction:

Improveprotection against Lassa feverVSAvoidvaccine development complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs a universal vaccine platform using NDV vectors that can be adapted to express different Lassa virus antigens (glycoprotein, nucleoprotein, or chimeric proteins). This multi-functional approach allows a single vaccine platform to address multiple antigen targets, simplifying the overall development process compared to creating separate vaccines for each antigen

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent utilizes composite viral structures by combining the NDV vector backbone with Lassa virus antigen genes. The resulting recombinant virus combines the safety and manufacturability of NDV with the immunogenicity of Lassa virus antigens, creating a composite vaccine that addresses both safety and efficacy requirements

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS20250250304A1Recombinant newcastle disease virus expressing lassa virus GP or NP, and uses thereof

Publication Date: 2025.08.07 BERNHARD NOCHT INST FUR TROPENMEDIZIN

AI summary

Provided herein are polynucleotides encoding Lassa virus glycoprotein or Lassa virus nucleoprotein, or a chimeric protein comprising the ectodomain of Lassa virus glycoprotein and the transmembrane and cytoplasmic domains of NDV F protein. Also, provided herein are recombinant Newcastle disease virus (NDV) comprising such a polynucleotide, and immunogenic compositions comprising such recombinant NDV. Further, provided herein are methods for immunizing against Lassa virus comprising administering the recombinant NDV or an immunogenic composition thereof.