Methods and compositions for assessing antibody specificities
Inventors
Daugherty, Patrick Sean • Kamath, Kathryn Vinaya Louise • Reifert, Jack Ryan
Assignees
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Publication Number
US-12146884-B2
Publication Date
2024-11-19
Expiration Date
Abstract
The present invention provides compositions and methods that can be used to determine a peptide signature for an antibody repertoire in a sample comprising multiple antibodies. The method can be used to characterize a phenotype in a sample, such as providing a diagnosis, prognosis or theranosis of a medical condition.
Core Innovation
The invention relates to array-based diagnostics that determine antibody specificity signatures and phenotype using peptide binding motifs. The approach provides an array that presents one or more peptides on an array surface for binding by antibodies in a biological sample, and uses the binding pattern across motif peptides as the antibody specificity signature.
An array presents an antibody binding motif using a short peptide. The peptide comprises a binding motif sequence LxGM[RQ]K (SEQ ID NO: 365) with a length of 30 amino acids or less, and the peptide is operably linked to an array surface to present the peptide for binding by an antibody. The array surface comprises either a solid surface with the peptide attached, or a biological particle engineered to express the peptide operably linked to a display scaffold that displays the peptide on an outer surface, where the amino acid sequence of the peptide is heterologous to the biological particle.
A further array comprises at least two peptides presented for binding by one or more antibodies. The first peptide includes the binding motif sequence LxGM[RQ]K (SEQ ID NO: 365) and the second peptide includes a binding motif selected from multiple motif sequences. A computational component evaluates motif enrichment and motif discovery to generate multiplex motif panels and phenotype determinations, including alignment and clustering approaches such as MEME and an NGS-oriented IMUNE algorithm.
Claims Coverage
The independent claims cover two related array structures that present motif-containing peptides for antibody binding. The claims include at least two inventive features, centered on a short LxGM[RQ]K peptide array on a solid surface or engineered biological particle, and a multiplex array with a second motif selected from a defined group.
Motif peptide array with LxGM[RQ]K peptide on an array surface
An array comprising a peptide having a binding motif sequence LxGM[RQ]K (SEQ ID NO: 365) with a length of 30 amino acids or less, operably linked to an array surface for binding by an antibody, where the array surface comprises a solid surface with peptide attached or a biological particle engineered to express the peptide operably linked to a display scaffold that displays the peptide on an outer surface, with the peptide sequence heterologous to the biological particle.
Multi-motif peptide array with LxGM[RQ]K plus selectable motif peptides
An array comprising at least two peptides: a first peptide with binding motif sequence LxGM[RQ]K (SEQ ID NO: 365) and a second peptide with a binding motif selected from a specified group of motif patterns, where each peptide is operably linked to an array surface for binding by one or more antibodies, and the array surface comprises either a solid surface with both peptides attached or first and second engineered biological particles each expressing the respective peptide operably linked to a display scaffold displaying the respective peptide on the outer surface with heterologous amino acid sequences.
Claim coverage centers on arrays that present antibody binding motif peptides, including LxGM[RQ]K and additional selectable motifs, on either solid surfaces or engineered biological particles using display scaffolds and heterologous peptide sequences.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Detecting antibodies associated with a Borrelia burgdorferi infection by contacting an array of motif-presenting peptides with a biological sample containing antibodies, incubating for peptide-antibody binding, and measuring peptide binding to indicate infection positivity.
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