Fc-Modified CSP Antigen-Binding Proteins for Malaria Prophylaxis
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Solution Overview
Problem
Current malaria vaccines and treatments face challenges in providing robust immune protection due to difficulties in identifying effective mechanisms and administration issues in malaria-endemic regions, with existing antibodies lacking Fc-mediated effector functions and prolonged efficacy.
Innovation Solution
Development of Plasmodium falciparum circumsporozoite protein (CSP) antigen binding proteins with modified Fc regions to enhance antibody-dependent cellular phagocytosis (ADCP) and antibody-dependent NK cell activation (ADNKA), combined with increased half-life modifications, to provide enhanced immune protection against malaria.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing antibodies are used for malaria prevention, then they can bind to CSP, but they lack Fc-mediated effector functions and prolonged efficacy
Solution Approach 1:
The patent applies parameter changes by modifying the Fc region of antibodies through specific amino acid substitutions (e.g., L234Y, L235Q, G236W, S239M, H268D, D270E, S298A, E333A, K334E) to enhance effector functions and extend half-life. These parameter modifications transform standard antibodies into optimized therapeutic agents with improved protective efficacy and prolonged duration of action against malaria.
2Reliability
If malaria vaccines are administered in malaria-endemic regions, then they aim to provide immune protection, but administration issues and difficulty in identifying effective mechanisms reduce their effectiveness
Solution Approach 1:
The patent employs disposable single-dose pre-filled syringes containing the optimized antibody formulation. This approach eliminates the need for complex cold chain storage and multiple administrations, making the intervention highly feasible in resource-limited malaria-endemic regions while maintaining reliable immune protection.
3Reliability
If Fc region modifications are made to enhance effector function, then antibody-dependent cellular phagocytosis and NK cell activation are improved, but the complexity of antibody structure increases
Solution Approach 1:
The patent applies local quality by making targeted amino acid substitutions specifically in the Fc region of the antibody while leaving the antigen-binding Fab regions unchanged. This localized modification approach enhances effector functions (ADCP, ADNKA) and extends half-life without affecting antigen binding, thereby improving reliability while minimizing structural complexity increases.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The modified CSP antigen binding proteins demonstrate improved efficacy by activating host immune responses, targeting antigen-presenting cells, and maintaining serum concentration, offering effective prophylaxis against malaria with reduced administration frequency.
Implementation Method 1
enhance antibody-dependent cellular phagocytosis (ADCP)
Implementation Method 2
enhance antibody-dependent NK cell activation (ADNKA)
Implementation Method 3
Plasmodium falciparum circumsporozoite protein (CSP) antigen binding proteins
Data Source
AI summary
The present invention provides antigen binding proteins such as antibodies targeting Plasmodium sporozoites, in particular Plasmodium circumsporozoite protein. The invention also provides nucleic acids that encode such antibodies. In addition, the invention provides antibodies according to the invention for use in the prophylaxis of malaria.