Simian Adenovirus Vectors Evading Pre-existing Immunity

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Solution Overview

Problem

Current adenovirus vectors face challenges in effectively delivering molecules to target cells while minimizing the impact of pre-existing immunity in the population, particularly due to existing adenovirus serotypes.

Innovation Solution

Development of novel simian adenovirus vectors, including SAdV-A1321, SAdV-A1325, SAdV-A1295, SAdV-A1309, and SAdV-A1322, which provide isolated nucleic acid and amino acid sequences for creating adenoviral vectors that can deliver heterologous genes and proteins, offering alternative immune responses and helper functions for adenovirus-associated viral vectors.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional adenovirus vectors are used for gene delivery, then efficient gene transfer is achieved, but pre-existing immunity in the population interferes with effective delivery

Engineering Contradiction:
Improvegene delivery efficiencyVSAvoidpre-existing immunity interference
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention segments the adenovirus vector system by creating distinct serotypes (A1321, A1325, A1295, A1309, A1316, A1322) with unique capsid proteins. This segmentation allows each serotype to evade pre-existing immunity targeting other serotypes, thereby maintaining gene delivery efficiency despite population immunity to conventional adenoviruses.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention changes the serological parameters of the adenovirus vector by using novel simian adenovirus serotypes with distinct antigenic properties. This parameter change in viral identity allows the vectors to bypass neutralizing antibodies generated against human adenovirus serotypes, resolving the contradiction between delivery efficiency and immunity interference.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If human adenovirus serotypes are used for vaccination, then immune response can be elicited, but pre-existing immunity limits effectiveness

Engineering Contradiction:
Improvevaccine effectivenessVSAvoidpre-existing adenovirus immunity
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

Instead of using human adenovirus serotypes for vaccination, the invention inverts the approach by using simian adenovirus serotypes that are antigenically distinct. This inversion allows the vaccine vectors to escape pre-existing human immunity while still capable of eliciting protective immune responses against target antigens.

Inventive Principle:
Principle #13The other way round (Inversion)

Solution Approach 2:

The simian adenovirus vectors serve as an intermediary delivery system that carries vaccine antigens without being recognized by pre-existing human anti-adenovirus immunity. This intermediary approach allows effective vaccine delivery by decoupling the delivery vehicle (simian adenovirus) from the target antigen (human pathogen antigen).

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentUS10149873B2Subfamily E simian adenoviruses A1321, A1325, A1295, A1309, A1316 and A1322 and uses thereof
Publication Date: 2018.12.11 THE TRUSTEES OF THE UNIV OF PENNSYLVANIA

AI summary

Recombinant vectors comprise simian adenovirus A1321 (SAdV-A1321), SAdV-A1325, SAdV-A1295, SAdV-A1309, SAdV-A1316, and/or SAdV-A1322 sequences and a heterologous gene under the control of regulatory sequences. A cell line which expresses simian adenovirus SAdV-A1321, SAdV-A1325, SAdV-A1295, SAdV-A1309, SAdV-A1316, and/or SAdV-A1322 gene(s) is also disclosed. Methods of using the vectors and cell lines are provided.