Multivalent BKV Vaccine Elicits Broad Immune Response

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Solution Overview

Problem

Current methods for managing polyomavirus-associated pathologies in transplant patients, such as PVAN and PML, are inadequate due to limited cross-reactivity of anti-BKV antibodies between serotypes, leading to insufficient protection and increased risk of infection with less common serotypes like BKV-IV.

Innovation Solution

Development of multivalent immunogenic compositions including capsid polypeptides from multiple BKV serotypes and JC virus, administered to elicit a broad immune response and neutralizing antibodies, along with methods to select transplant donors and recipients based on serotype-specific neutralizing antibodies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If monovalent immunogenic compositions targeting a single BKV serotype are used, then the immune response is focused and potent against that specific serotype, but protection against other serotypes is insufficient due to limited cross-reactivity

Engineering Contradiction:

Improveprotection efficacy against targeted serotypeVSAvoidprotection coverage across multiple serotypes

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines capsid polypeptides from multiple BKV serotypes (including BKV-I, BKV-IV, and other less common serotypes) into a single multivalent immunogenic composition. This merging approach allows the vaccine to elicit broad immune responses that provide cross-protection against multiple serotypes simultaneously, resolving the contradiction between focused potency and broad coverage

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The multivalent composition serves multiple protective functions by incorporating antigens from different serotypes. A single vaccine administration provides universal protection against various BKV serotypes, making the immunogenic composition adaptable to diverse viral strains while maintaining reliable protection efficacy

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Reliability

If immunosuppressants are used to prevent rejection, then graft survival is improved, but the risk of polyomavirus reactivation and PVAN increases

Engineering Contradiction:

Improveallograft survivalVSAvoidpolyomavirus reactivation risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent administers the multivalent immunogenic composition to transplant recipients before they begin immunosuppressive therapy or at the time of transplantation. This preliminary vaccination establishes protective immunity against BKV prior to immune suppression, creating a buffer that reduces the risk of viral reactivation and PVAN development during the immunosuppressed state

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The vaccine provides a protective buffer or cushion against BKV infection by pre-establishing neutralizing antibodies and immune memory cells. This beforehand cushioning allows patients to tolerate necessary immunosuppression for graft survival while having pre-formed immune defenses that can quickly respond to any viral reactivation attempts

Inventive Principle:

Principle #11Beforehand cushioning (Prior cushioning)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

The approach effectively elicits a robust immune response against multiple BKV serotypes and reduces the risk of polyomavirus-associated pathologies by providing protection against a broader range of BKV strains, including less common types like BKV-IV, thereby improving transplant outcomes.

Implementation Method 1

eliciting an immune response against a polyomavirus (for example, BKV serotype I (BKV-I), BKV serotype II (BKV-II), BKV serotype III (BKV-III), and/or BKV serotype IV (BKV-IV))

Methodology Applied

Scientific EffectImmune response:

Implementation Method 2

methods of treating or inhibiting polyomavirus-associated pathology (such as PVAN, BKV-associated hemorrhagic cystitis, or JC virus-associated PML)

Methodology Applied

Scientific EffectNeutralizing antibodies:

Data Source

PatentEP2734544B1Methods and compositions for inhibiting polyomavirus-associated pathology

Publication Date: 2020.12.16 THE GOVERNMENT OF THE UNITED STATES OF AMERICA AS REPRESENTED BY THE SECRETARY DEPARTMENT OF HEALTH & HUMAN SERVICES

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AI summary

Disclosed herein are methods of eliciting an immune response against a polyomavirus (for example, BKV serotype I (BKV-I), BKV serotype II (BKV-II), BKV serotype III (BKV-III) and/or BKV serotype IV (BKV-IV)) and methods of treating or inhibiting polyomavirus-associated pathology (such as polyomavirus- associated nephropathy, BKV- associated hemorrhagic cystitis, or JC virus-associated progressive multifocal leukoencephalopathy; PML). Further disclosed are immunogenic compositions of use in the disclosed methods. Also disclosed are methods of selecting an organ transplant donor and/or recipient including detecting whether the prospective donor and/or recipient has BKV serotype-specific (such as BKV serotype IV-specific) neutralizing antibodies.