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Systems and methods of epitope binning and antibody profiling

a monoclonal antibody and epitope mapping technology, applied in the field of epitope mapping and monoclonal antibody profiling, can solve the problems of requiring costly synthesis or enrichment steps, standard methods developed for mapping antibody epitopes, bacteria, mrna display,

Inactive Publication Date: 2021-03-25
ARIZONA STATE UNIVERSITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This approach enables high-throughput, cost-effective epitope mapping and monoclonal antibody profiling, allowing for the identification of specific binding sites and protein targets, thereby facilitating the development of therapeutic antibodies.

Problems solved by technology

Unfortunately, standard methods developed for mapping antibody epitopes, including peptide tiling and phage, bacteria, and mRNA display, require costly synthesis or enrichment steps.
At present, no low-cost universal platform for screening monoclonal antibodies exists.

Method used

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  • Systems and methods of epitope binning and antibody profiling
  • Systems and methods of epitope binning and antibody profiling
  • Systems and methods of epitope binning and antibody profiling

Examples

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Comparison scheme
Effect test

example 1

Epitope Determination in Monoclonal Antibodies

[0077]Experiments were designed to determine whether one could predicatively map epitopes to well-characterized monoclonal antibodies. Eight antibodies with reactivity to a known linear sequence were chosen and analyzed.

[0078]Table 1 lists peptides and binding intensities for the eight different monoclonal antibodies. Monoclonal antibodies were used to test the motif search analysis algorithm. The highest rated subsequences were related to the true epitope and to each other to an extent that ensured the emergence of a conserved motif with strong association to the epitope sequence. Ab, antibody; GRAVY, grand average of hydropathicity index (Legutki J. B., Nat. Commun. 5:4785, (2014)).

TABLE 1Monoclonal antibodies used in this studyMeanMappedAbsignalpredic-EpitopenameImmunogenIsotypepIGRAVYintensityativelyEEDFRVA10Human Pol IIIgG2b4.1−1.34911NoSDLWKLp53ab8Human p53IgG2b,5.6−0.36243NoIgG2aQAFDSH4C1HumanIgG2a5.1−1.1971YesinsulinreceptorRHSVV...

example 2

Groupwise Epitope Determination in Patient Sera

[0088]Eight cohorts representing seven different diseases and one group of healthy volunteers were tested using the described methods.

[0089]FIG. 5A shows the top 10 most commonly appearing and significant subsequences in serum samples from the indicated disease cohorts. The number of patients within that cohort for which that sequence was called significant is shown in parentheses to the left. The y-axis is categorical and shows each subsequence; the x-axis is the maximum log 10-normalized intensity of the peptide binding on the array for each patient. The total number of samples in each cohort is given as a fraction at the top. Subsequences with exact matches to proteins within the pathogen are indicated with vertical red bars. The top ranked sequences are listed in Table 3 that shows discovered epitope sequences and their proposed antigen mappings as described below (Example 3).

TABLE 3Proposed epitope mappings for disease cohortsKnown...

example 3

Identification of Consensus Sequences in Pathogen Proteomes

[0092]In order to test whether the groupwise consensus motifs (FIGS. 4A-B) corresponded with true epitopes, the Immune Epitope Database was searched for exact substring matches to sequences from these lists. Despite the small size of this database, the sequence AVHAD from dengue was present in the database and indicated as an epitope from the NS1 protein in two dengue strains (E-value: 5×10−4).

[0093]Further analysis of the other cohorts revealed additional matches to antigenic proteins. The sequence EDAK from Borrelia mapped to known antigen OspF (E-value: 4.6), and DYAFG from syphilis mapped to a lipoprotein in several strains of T. pallidum (E-value: 0.27). Malaria contained sequences SNKQG and RLKEP (FIG. 7), both of which mapped to the ring-infect erythrocyte surface antigen (RESA) protein in P. falciparum 3D7 (E-value: 0.072), and another sequence (DAFEY) mapping to one of the pfEMP1 variants in P. falciparum (E-value: ...

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Abstract

Methods for antibody profiling and epitope mapping are provided herein. More particularly, methods for screening and mapping epitopes of candidate antibodies and protein target identification are provided herein.

Description

CROSS-REFERENCE[0001]This application claims the benefit of U.S. Provisional Application No. 62 / 160,276, filed on May 12, 2015, which is entirely incorporated herein by reference.BACKGROUND[0002]This invention relates to methods and systems for developing therapeutic affinity reagents. More particularly, the present invention provides methods and systems for epitope mapping and monoclonal antibody profiling.[0003]Antibodies play a central role in the immune system and in modern health care and medical research. They are commonly used as affinity reagents in research and diagnostic applications and have emerged as an important class of therapeutics. In particular, the development of monoclonal antibody (mAb) technology has had a profound impact on medicine. The therapeutic use of first-generation mAb achieved considerable success in the treatment of major diseases, including cancer, inflammation, autoimmune, cardiovascular, and infectious diseases. It is estimated that the majority o...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): G01N33/68
CPCG01N33/6878
Inventor JOHNSTON, STEPHEN ALBERT
Owner ARIZONA STATE UNIVERSITY
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