Chimeric Lyssavirus Glycoprotein Vaccine Broadens Neutralizing Antibody Coverage

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Solution Overview

Problem

Current rabies vaccines only protect against classical rabies virus and closely-related species, failing to provide immunity against more distant and emerging lyssaviruses, which are classified into Phylogroups II and III, leaving a gap in protection against a spectrum of rabies-causing viruses.

Innovation Solution

Development of chimeric lyssavirus glycoproteins combining components from different lyssaviruses, such as RABV and MOKV, inserted into a rabies-based vaccine vector, offering broader protection by eliciting a cross-reactive immune response across multiple lyssavirus species.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current rabies vaccines (HDCV or PCECV) are used, then protection against classical rabies virus and closely-related species is achieved, but protection against more distant and emerging lyssaviruses (Phylogroups II and III) is lost

Engineering Contradiction:

Improveprotection coverageVSAvoidbreadth of lyssavirus coverage

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines glycoprotein genes from multiple lyssavirus species (Phylogroup I, II, and III) into a single chimeric glycoprotein construct. This merged antigen contains epitopes from diverse lyssaviruses including RABV, MOKV, LBV, DUVV, EBLV-1, EBLV-2, IRKV, and WCBV, enabling a single vaccine to elicit cross-protective immune responses against all these viruses simultaneously

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The chimeric glycoprotein vaccine is designed to provide universal protection against all known lyssavirus phylogroups. The single vaccine formulation functions against multiple virus types by incorporating conserved and variable epitopes from different lyssavirus species, making it a multi-functional vaccine that replaces the need for separate vaccines for different lyssavirus strains

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Adaptability or versatility

If chimeric glycoprotein vaccine is developed to broaden protection, then coverage against Phylogroups II and III is improved, but vaccine complexity increases

Engineering Contradiction:

Improvelyssavirus phylogroup coverageVSAvoidvaccine construct complexity

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The chimeric glycoprotein is constructed by segmenting and recombining specific domains from different lyssavirus glycoproteins. The construct includes signal peptide, clip, core, flap, transmembrane, and cytoplasmic domains from various lyssavirus species, with strategic placement of epitopes from Phylogroups I, II, and III to achieve broad coverage while maintaining structural integrity

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The vaccine uses a composite glycoprotein structure that integrates antigenic determinants from multiple viral sources. The chimeric construct combines hydrophobic domains, transmembrane regions, and cytoplasmic tails from different lyssaviruses into a single functional protein that can be expressed as a unified vaccine antigen

Inventive Principle:

Principle #40Composite materials

3Reliability

If DNA immunization is used to test chimeric G protection, then protection against both RABV and MOKV is achieved, but translatability into vaccine potential is limited

Engineering Contradiction:

Improvedual virus protectionVSAvoidvaccine translatability

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent creates a viral vector system that copies the successful DNA immunization approach by expressing chimeric glycoproteins in a replicating viral platform. The rabies virus-based vector naturally expresses the chimeric G protein during replication, copying the protective effect of DNA immunization while using a more translatable viral vaccine platform that mimics natural infection dynamics

Inventive Principle:

Principle #26Copying

Data Source

PatentUS11484586B2Compositions and administration of chimeric glycoprotein lyssavirus vaccines for coverage against rabies

Publication Date: 2022.11.01 THOMAS JEFFERSON UNIV

AI summary

The present disclosure is directed towards chimeric glycoproteins wherein the clip region, a core region, a flap region, and a transmembrane and cytoplasmic domain are defined by starting from the amino terminus of the protein, these domains are comprised of the following amino acid residue ranges: clip, 1 through 40 to 60; core, 40 to 60 through 249 to 281; flap, 249 to 281 through 419 to 459; the transmembrane domain is comprised of amino acids 460 through 480, and the remaining amino acids 481 through 525 comprise the cytoplasmic domain; and wherein the clip, core, flap, transmembrane, and cytoplasmic domain comprise a chimeric combination of at least two lyssavirus, wherein the chimeric glycoprotein is advantageously inserted into a rabies-based vaccine vector.