Basigin-Binding VHH Antibodies for Blocking Malaria RBC Entry

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current treatments for malaria, particularly caused by Plasmodium falciparum, face challenges such as the emergence of resistant strains and the persistence of parasitized red blood cells post-treatment, leading to prolonged symptoms and high mortality, while existing vaccines only protect against the liver stage and not the blood stage of the parasite.

Innovation Solution

Development of single-domain VHH antibodies targeting basigin to block the interaction between Plasmodium falciparum and erythrocytes, which are highly affine and thermostable, allowing for both diagnostic and therapeutic applications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If full-sized antibodies are used to target basigin, then blocking efficacy against Plasmodium falciparum is achieved, but risk of hemolysis through opsonisation and complement activation increases

Engineering Contradiction:

Improveblocking efficacyVSAvoidhemolysis risk

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and utilizes only the variable heavy chain domain (VHH) of the antibody, which contains the antigen-binding site, while removing the Fc region that mediates complement activation and opsonisation. This single-domain antibody fragment maintains the ability to bind basigin and block PfRH5 interaction while eliminating the harmful Fc-mediated effects that cause hemolysis.

Inventive Principle:

Principle #2Taking out (Extraction)

2Reliability

If antibodies against PfRH5 are used, then parasite propagation is reduced, but therapeutic efficacy is limited by short exposure time and kinetic competition with basigin

Engineering Contradiction:

Improveparasite propagation reductionVSAvoidexposure time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent employs preliminary action by pre-blocking the basigin receptor on erythrocyte surfaces with VHH antibodies before Plasmodium falciparum merozoites attempt to invade. This prevents the parasite from binding to basigin in the first place, eliminating the need to compete kinetically during the brief invasion window and ensuring effective blockade regardless of the short exposure time available during the invasion process.

Inventive Principle:

Principle #10Preliminary action

3Reliability

If current therapeutics are administered, then parasite viability is reduced, but parasitized RBCs persist leading to prolonged symptoms

Engineering Contradiction:

Improveparasite viability reductionVSAvoidparasitized RBC persistence

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent converts the previously harmful or useless parasitized RBCs into beneficial tools for vaccination and diagnostics. By using VHH antibodies that specifically bind to basigin on the surface of parasitized RBCs, these cells can be detected, isolated, and used as antigen sources for developing vaccines or as diagnostic markers, thereby transforming the persistence problem into a useful resource.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentEP4682167A1Therapeutic variable domain of heavy chain (VHH) antibodies against basigin (CD147) and their use for blocking plasmodium falciparum entry into human erythrocytes

Publication Date: 2026.01.21 MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN EV

Figure 1
Figure 1
Figure 2

AI summary

The present invention pertains to the fields of antibody technology, medicine, pharmacology, infection biology, and virology. More specifically, the present disclosure provides VHH antibodies that prevent erythrocyte entry of and infection by Plasmodium falciparum.