RSV F-Specific Antibodies for Prefusion Neutralization in Infants
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Solution Overview
Problem
Current RSV vaccines and monoclonal antibodies are costly, require multiple doses, and are only modestly efficacious, with infants presenting unique challenges such as suppression of B cell responses by maternal antibodies and immunological immaturity, limiting their availability in developing countries and effectiveness in high-risk populations.
Innovation Solution
Isolation and characterization of a panel of RSV F-specific monoclonal antibodies from infants, recognizing distinct antigenic sites and displaying potent neutralizing activity, facilitating the design of vaccine antigens that elicit desired B cell responses in infants, including high-affinity binding to prefusion F and neutralizing antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If passive prophylaxis with monoclonal antibody Synagis is used, then protection against RSV is provided, but cost is high and multiple doses are required
Solution Approach 1:
The patent applies preliminary action by developing vaccines that induce long-lasting immunity before RSV season begins, eliminating the need for repeated prophylactic doses during the season. The vaccine candidates prime the immune system in advance to provide sustained protection throughout the RSV season and beyond.
Solution Approach 2:
The patent employs parameter changes by modifying the immunogenicity and persistence of immune responses through optimized vaccine formulations. By changing parameters such as antigen presentation methods and adjuvant selection, the vaccines achieve extended duration of protection, reducing the frequency of administration from monthly to annual or longer intervals.
2Reliability
If RSV vaccines are developed to induce neutralizing antibodies, then protection is improved, but vaccine-enhanced disease risk increases
Solution Approach 1:
The patent applies local quality by directing the immune response toward specific epitopes on the RSV F glycoprotein, particularly the prefusion conformation. By focusing antibody production on particular antigenic sites through specialized vaccine designs, the immune response achieves high neutralizing activity without triggering harmful enhancement effects associated with broader or inappropriate immune responses.
Solution Approach 2:
The patent converts the potential harm of vaccine-enhanced disease into benefit by using controlled immunization strategies that induce protective immunity while avoiding pathological responses. The vaccine designs incorporate mechanisms to ensure antibodies enhance clearance rather than facilitate viral entry, transforming what could be a harmful effect into a protective mechanism.
3Stability of the object's composition
If vaccines target postfusion conformation of RSV F, then antibody binding is stable, but neutralizing activity is reduced
Solution Approach 1:
The patent applies preliminary action by presenting the prefusion conformation of RSV F to the immune system before viral infection occurs. This allows antibodies to be generated that recognize and bind to the prefusion state, which is the conformation present on native virions and essential for neutralization, rather than the postfusion conformation that only appears after viral entry.
Solution Approach 2:
The patent employs parameter changes by stabilizing the prefusion conformation of RSV F through engineered mutations and formulation approaches. By modifying structural parameters of the F protein to lock it in the prefusion state, the vaccines elicit antibodies with both high affinity and potent neutralizing activity, overcoming the limitation of targeting the postfusion conformation.
Data Source
AI summary
Provided are antibodies or antigen binding polypeptides characterized by the ability to neutralize respiratory syncytial virus (RSV). Specifically, the antibodies or antigen binding polypeptides are characterized by high affinity binding to RSV fusion glycoprotein (RSVF). Further provided are methods for their identification, isolation, generation, preparation, and use, as well as the heavy chain and light chain sequences of the antibodies provided.