Epitope focusing by variable effective antigen surface concentration
Inventors
Assignees
Publication Number
US-12043647-B2
Publication Date
2024-07-23
Expiration Date
2033-05-21
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Abstract
The present disclosure provides compositions and methods for the generation of an antibody or immunogenic composition, such as a vaccine, through epitope focusing by variable effective antigen surface concentration. Generally, the composition and methods of the disclosure comprise three steps: a “design process” comprising one or more in silico bioinformatics steps to select and generate a library of potential antigens for use in the immunogenic composition; a “formulation process”, comprising in vitro testing of potential antigens, using various biochemical assays, and further combining two or more antigens to generate one or more immunogenic compositions; and an “administering” step, whereby the immunogenic composition is administered to a host animal, immune cell, subject or patient. Further steps may also be included, such as the isolation and production of antibodies raised by host immune response to the immunogenic composition.
Core Innovation
The invention provides compositions and methods for generating an antibody or immunogenic composition, such as a vaccine, through epitope focusing by variable effective antigen surface concentration. The disclosed approach involves a design process using in silico bioinformatics to select and generate a library of potential antigens, a formulation process that tests and combines antigens based on biochemical assays, and an administering step in which the optimized immunogenic composition is delivered to a host, immune cell, subject, or patient. Additional steps such as the isolation and production of antibodies raised by host immune response to the immunogenic composition may be included.
The problem addressed arises from the ability of pathogens, including viruses and bacteria, to evade host immune responses through antigenic variation and drift in immunodominant epitopes, which undermines vaccine effectiveness. Traditional vaccine approaches are compromised because early neutralizing antibodies become ineffective due to mutations, and immunodominant epitopes may mask other, more conserved epitopes of potential value. There is a need for novel methods to generate antibodies to specific or highly conserved epitopes for broad and effective protection, especially against pathogens like HIV-1 and influenza, where current vaccines are insufficient.
The innovation achieves selective stimulation of immune responses to a specific, conserved epitope by formulating a mixture of at least six different antigens, each encoding a common target epitope, but where each antigen is present at an individual level insufficient to be immunogenic alone. This results in higher effective concentration of the target epitope and greater immune focus on that region. Computational tools are used to ensure sequence diversity in the non-target regions while retaining conservation within the target epitope, and the ensemble is manufactured and delivered as a nucleic acid vaccine or protein mixture, optionally including further agents for immune targeting or stimulation.
Claims Coverage
There are two independent claims in the patent, each directed to a distinct inventive feature.
Nucleic acid vaccine encoding at least six different antigens sharing a common target epitope and individual antigen expression levels insufficient for immunogenicity
A nucleic acid vaccine composition is disclosed which contains one or more nucleic acids encoding at least six different antigens. Each antigen comprises a common target epitope. Upon administration, each individual antigen is expressed at a level that, by itself, is insufficient to elicit an immune response.
Method of treating or reducing likelihood of disease by administering nucleic acid vaccine encoding at least six different antigens sharing a common target epitope, with individual antigen expression levels insufficient for immunogenicity
A method is provided for treating or reducing the likelihood of a disease in a human subject in need thereof. The method involves administering the nucleic acid vaccine (as defined above) to the subject, resulting in treatment or reduced risk of disease. The vaccine comprises at least six different antigens, each comprising a common target epitope, and each being expressed at a non-immunogenic level when administered individually.
The inventive features cover a nucleic acid vaccine comprising at least six different antigens with a shared target epitope and non-immunogenic expression of each antigen alone, and a method of disease treatment or prevention using such a vaccine.
Stated Advantages
The immunogenic composition enables selective immune response to conserved or desired epitopes, reducing immune response to variable, non-targeted regions of antigens.
The approach addresses antigenic variation and drift by focusing the immune system on epitopes less subject to mutation, potentially improving vaccine efficacy against highly variable pathogens.
Non-target epitope regions are diversified such that only the common target epitope is immunogenically recognized, supporting broader or more robust protection.
Individual antigen variants are present at concentrations insufficient to elicit an immune response on their own, minimizing off-target effects and focusing immunity on the epitope of interest.
Documented Applications
Development of vaccines for prevention and/or treatment of a variety of human diseases, including infectious diseases from viruses, bacteria, parasites, and cancer.
Generation of antibodies directed to a single epitope of interest for antibody-based tools and therapies, such as for identification, detection, diagnosis, or treatment of diseases.
Use in generating antibody-based tools for research purposes, including immunoassays, protein purification, identification, quantification, and structural mapping.
Treatment or reduction of likelihood of diseases such as infectious diseases, autoimmune diseases, inflammatory diseases, neurological diseases, addiction, cardiovascular diseases, endocrine diseases, and cancer.
Use in producing antibodies for diagnostic assays to detect antibody presence or absence.
Use as a nucleic acid vaccine to elicit an immune response in a subject by administration of the nucleic acid vaccine as described.
Interested in licensing this patent?