Recombinant Polypeptide Vaccines for MAP Infection Control
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Solution Overview
Problem
Mycobacterium avium subspecies paratuberculosis (MAP) infections are difficult to eradicate due to the organisms' slow growth, low abundance, and resistance to standard detection methods and anti-TB drugs, particularly in cases of Crohn's disease and Irritable Bowel Syndrome, where they cause chronic inflammation and are often systemic.
Innovation Solution
Development of specific polypeptides and polynucleotides, such as ahpC, gsd, p12, and mpa, which can induce a therapeutic or prophylactic immune response by encoding epitopes that stimulate an immune reaction against MAP, using vectors like poxvirus, adenovirus, and plasmids for expression and delivery.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard anti-TB drugs are used to treat MAP infections, then treatment is attempted, but the drugs are ineffective due to MAP's resistance
Solution Approach 1:
The patent changes the therapeutic approach from conventional anti-TB drugs to recombinant polypeptide vaccines that target specific MAP antigens (MPB64, MPB70, MPB83, MPB84). This parameter change in treatment modality overcomes the drug resistance problem by using an entirely different mechanism - immune system activation rather than direct bacterial killing.
Solution Approach 2:
The patent introduces recombinant polypeptides as intermediaries that bridge the gap between the host immune system and MAP bacteria. These polypeptide vaccines act as mediators that stimulate the immune system to recognize and attack MAP, bypassing the ineffective direct drug-bacteria interaction.
2Measurement precision
If conventional culture methods are used to detect MAP, then detection is attempted, but the methods fail due to slow growth and low abundance
Solution Approach 1:
The patent extracts specific antigenic components (MPB64, MPB70, MPB83, MPB84 polypeptides) from the complex MAP organism and uses them as diagnostic and therapeutic targets. This extraction allows detection and treatment without requiring large numbers of live bacteria, overcoming the slow growth limitation.
Solution Approach 2:
The patent creates recombinant copies of specific MAP antigens in heterologous expression systems (bacterial, insect, or mammalian cell lines). These copied antigens can be produced in large quantities without requiring MAP to grow, enabling sensitive detection and abundant supply for therapy.
3Measurement precision
If MAP organisms are present in low abundance and adopt ZN negative form, then detection is attempted, but ordinary light microscopy cannot see them
Solution Approach 1:
The patent replaces the mechanical/optical detection system (light microscopy requiring ZN positive staining) with a molecular recognition system using polypeptide-specific antibodies or antigen-specific T cell responses. This substitution enables detection of MAP antigens regardless of bacterial morphology or staining properties.
Data Source
AI summary
The present invention relates to molecules, which can be used to induce a therapeutic or prophylactic immune response against MAP. In particular, the present invention relates to polypeptides comprising an alipC polypeptide sequence, a gsd polypeptide sequence, a p12 polypeptide sequence and an mpa polypeptide sequence, wherein said ahpC polypeptide comprises the sequence of SEQ ID NO: 2, a variant thereof having more than 70% amino acid sequence identity to SEQ ID NO: 2 across the full length of SEQ ID NO: 2, or a fragment of at least 8 amino acids of SEQ ID NO: 2 which comprises an epitope; said gsd polypeptide comprises the sequence of SEQ ID NO: 6, a variant thereof having more than 70% amino acid sequence identity to SEQ ID NO: 6 across the full length of SEQ ID NO: 6, or a fragment of at least 8 amino acids of SEQ ID NO: 6 which comprises an epitope; said pi 2 polypeptide comprises the sequence of SEQ ID NO: 10, a variant thereof having more than 70% amino acid sequence identity to SEQ ID NO: 10 across the full length of SEQ ID NO: 10, or a fragment of at least 8 amino acids of SEQ ID NO: 10 which comprises an epitope; and said mpa polypeptide comprises the sequence of SEQ ID NO: 14, a variant thereof having more than 70% amino acid sequence identity to SEQ ID NO: 14 across the full length of SEQ ID NO: 14, or a fragment of at least 8 amino acids of SEQ ID NO: 14 which comprises an epitope. Preferably such a variant maintains the ability to generate an immune response against the unmodified polypeptide.