AAV Vector Delivery of Anti-Influenza Antibodies

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Solution Overview

Problem

Current influenza vaccines have limited efficacy, especially in elderly and immunocompromised patients, and are not effective against zoonotic strains that can lead to pandemics, with existing monoclonal antibodies requiring high concentrations and generating escape mutants.

Innovation Solution

A composition comprising non-replicating recombinant adeno-associated virus (AAV) vectors expressing anti-influenza A and B antibodies, specifically FI6 and CR8033, for passive immunization, which can be administered intranasally or intramuscularly, providing rapid protection and reducing the need for repeated administrations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If traditional influenza vaccines are used, then immune response is generated, but efficacy is limited in elderly and immunocompromised patients

Engineering Contradiction:

Improvevaccine efficacyVSAvoideffectiveness across different patient populations

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

Instead of using inactivated virus or antigen to stimulate immune response, the patent uses AAV vectors to directly deliver genetic instructions for producing neutralizing antibodies in the host. This inverted approach bypasses the need for functional immune response generation, directly providing protective antibodies even in immunocompromised patients who cannot mount adequate immune responses

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The patent introduces AAV vectors as an intermediary carrier to deliver antibody-encoding genetic material into host cells. The AAV vector acts as a mediator between the desired therapeutic effect (antibody production) and the host system, enabling sustained antibody expression without requiring the host's immune system to process and respond to traditional vaccine antigens

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If monoclonal antibodies are administered at high concentrations, then protection is achieved, but escape mutants are generated

Engineering Contradiction:

Improveprotection efficacyVSAvoidescape mutant generation

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent creates a dynamic, self-replenishing system where host cells continuously produce therapeutic antibodies through AAV-mediated genetic expression. This dynamic production maintains consistent antibody levels without the need for repeated high-dose administrations, thereby preventing the selection pressure that leads to escape mutant development while ensuring sustained protection

Inventive Principle:

Principle #15Dynamics

Solution Approach 2:

The host's own cells are transformed into antibody-producing factories through AAV transduction. The system becomes self-sustaining, with endogenous cellular machinery continuously synthesizing and secreting neutralizing antibodies. This self-service approach eliminates the need for external antibody supplementation and prevents the harmful effects of high-concentration monoclonal antibody administration

Inventive Principle:

Principle #25Self-service

3Duration of action of moving object

If repeated vaccine administrations are given, then immunity is maintained, but frequency of administration increases

Engineering Contradiction:

Improveimmunity durationVSAvoidadministration frequency

Core Design Contradiction:

Duration of action of moving objectVSProductivity

Solution Approach 1:

The AAV vector establishes continuous antibody production by integrating or maintaining the antibody-encoding genetic material in host cell genomes or as episomes. This creates a persistent source of neutralizing antibodies that continues to protect the host over extended periods, eliminating the need for repeated administrations and maintaining continuous immune protection

Inventive Principle:

Principle #20Continuity of useful action

Data Source

PatentUS11535665B2AAV-mediated expression of anti-influenza antibodies and methods of use thereof

Publication Date: 2022.12.27 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA

AI summary

AAV vectors expressing anti-influenza antibodies are provided. Also described are pharmaceutical compositions useful in delivery same for prophylactic or anti-viral purposes. Methods of delivering such vectors are provided.