Membrane-Bound CD163 Antibodies for PRRSV Entry Blocking
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Solution Overview
Problem
Current treatments for Porcine Reproductive and Respiratory Syndrome (PRRS) virus (PRRSV) infections, such as genetic knockout of CD163 and vaccines, are complex, time-consuming, or have limited efficacy due to high genetic diversity and safety concerns, with no effective anti-viral options available.
Innovation Solution
Development of antibodies that specifically bind to the membrane-bound form of porcine CD163, avoiding soluble forms, to target and inhibit PRRSV infection, with enhanced efficacy when combined with other CD163 antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If genetic knockout of CD163 is used to treat PRRSV infections, then resistance to PRRSV infection is achieved, but the treatment becomes complex and time-consuming
Solution Approach 1:
The patent extracts and targets the specific CD163 receptor on cell surfaces using antibodies, rather than attempting genetic modification of the entire organism. This approach isolates the critical infection pathway (CD163-mediated viral entry) and blocks it specifically, achieving resistance without the complexity of genetic knockout procedures.
Solution Approach 2:
The patent introduces antibodies as intermediary molecules that bind to CD163 and prevent viral attachment. These antibodies act as mediators between the host immune system and the virus, providing a simpler alternative to direct genetic modification while maintaining effective protection against PRRSV infection.
2Reliability
If vaccines are used to treat PRRSV infections, then immunity is provided, but efficacy is limited due to high genetic diversity
Solution Approach 1:
The patent extracts the common functional element among diverse PRRSV strains - the requirement for CD163 binding for viral entry. By targeting this conserved cellular receptor rather than variable viral antigens, the approach overcomes the limitation of vaccine efficacy against genetically diverse strains.
Solution Approach 2:
Instead of trying to match vaccines to diverse viral strains (vaccine → virus), the patent inverts the approach by targeting the host cell receptor (CD163) that all PRRSV strains must use for entry (receptor → virus). This reversal provides broad-spectrum protection against genetically diverse strains.
3Reliability
If antibodies bind to soluble CD163, then they are neutralized, but they cannot effectively target membrane-bound CD163 on cells
Solution Approach 1:
The patent develops antibodies with localized binding specificity - they are designed to recognize and bind only to the membrane-bound form of CD163 on cell surfaces, not the soluble form in circulation. This local quality distinction (membrane-bound vs. soluble) enables precise targeting of the infectious pathway while avoiding neutralization by soluble CD163.
Solution Approach 2:
The patent exploits a key parameter difference between soluble and membrane-bound CD163 (their physical state and cellular context) to create antibodies that selectively bind to the membrane-bound form. This parameter-based differentiation allows the antibodies to maintain high reliability in binding to the relevant target while achieving manufacturing precision in specificity.
Data Source
AI summary
The present disclosure provides an antibody which binds to porcine CD163, wherein said antibody binds to the membrane-bound form of porcine CD163 on cells and does not bind significantly to the soluble form of porcine CD163. The present disclosure also provides a combination of said antibody with one or more further anti-porcine CD163 antibodies or binding proteins. Preferred combinations are those in which each antibody or binding protein binds to a different epitope in porcine CD163, and wherein said combination of anti-porcine CD163 antibodies or binding proteins are provided in a single construct. Nucleic acid molecules, expression vectors and compositions are also provided.