APMV3 Viral Vector Encoding Stabilized SARS-CoV-2 Spike Protein

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Solution Overview

Problem

There is an urgent need for effective vaccines and therapeutics to control the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and reduce the severity of COVID-19 symptoms.

Innovation Solution

The development of a paramyxovirus recombinant vector, specifically an avian paramyxovirus type 3 (APMV3) vector, that encodes for SARS-CoV-2 spike (S) protein or fragments thereof, including amino acid substitutions and proline substitutions, to induce an immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional vaccines and therapeutics are used, then some level of protection is provided, but they are insufficient to efficiently control SARS-CoV-2 spread and reduce severity

Engineering Contradiction:

Improveeffectiveness of vaccineVSAvoidcontrol of virus spread

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent modifies the SARS-CoV-2 spike protein by introducing six proline substitutions at positions 817, 892, 899, 942, 986, and 987. These parameter changes stabilize the spike protein in its prefusion conformation, enhancing immunogenicity and improving vaccine effectiveness while accelerating protective immune response development

Inventive Principle:

Principle #35Parameter changes

2Reliability

If multiple doses of vaccine are administered, then immune response is enhanced, but time and complexity increase

Engineering Contradiction:

Improveimmune response strengthVSAvoidvaccination time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The stabilized spike protein in the APMV3/S-6P vaccine is designed to pre-present the antigen in its most immunogenic prefusion conformation. This preliminary optimization of antigen structure enables the immune system to mount a strong response more quickly, reducing the time needed to achieve protective immunity and potentially allowing single-dose vaccination

Inventive Principle:

Principle #10Preliminary action

3Reliability

If the spike protein structure is modified with proline substitutions, then protein stability and immunogenicity are improved, but manufacturing complexity increases

Engineering Contradiction:

Improveprotein stabilityVSAvoidvector construction complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent uses an avian paramyxovirus type 3 (APMV3) as a viral vector to deliver the stabilized spike protein gene. This intermediary vector system simplifies manufacturing by using well-established avian virus production platforms, avoiding the need to directly manipulate complex eukaryotic expression systems while still achieving high-quality protein expression

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20250032603A1Expression of the spike s glycoprotein of SARS-COV-2 from avian paramyxovirus type 3 (APMV3)

Publication Date: 2025.01.30 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES

AI summary

Coronavirus spike protein, for example, SARS-CoV-2 spike (S) protein, expressed by an avian paramyxovirus type 3 (APMV3) as a vaccine vector for prevention and treatment against infection, such as SARS-CoV-2.