PfCSP Immunogen Composition Without KQ Motifs for Sustained Protection

Solution Overview

Problem

Current malaria vaccines, such as RTS,S/AS01, have limited efficacy and rapid waning of protection, highlighting the need for more effective immunogens and vaccine platforms targeting Plasmodium falciparum circumsporozoite protein (PfCSP) to enhance immune response and provide sustained protection.

Innovation Solution

Development of malarial immunogens comprising a portion of the wild-type PfCSP amino acid sequence lacking the KQ motif, combined with nanocage monomers like ferritin, and additional motifs like NPDPa, NANPb, and PADRE peptides to enhance immunogenicity and T-cell help, optionally with glycosylation and self-assembling into nanocages.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If RTS,S/AS01 vaccine containing 18.5 CSP NANP repeats and complete C-terminal domain is used, then initial protection is achieved, but efficacy wanes rapidly

Engineering Contradiction:

Improvevaccine efficacyVSAvoidprotection duration

Core Design Contradiction:

ReliabilityVSDuration of action of stationary object

Solution Approach 1:

The patent extracts and removes the KQ motif from the PfCSP amino acid sequence to create an improved immunogen. This extraction of the problematic KQ motif eliminates the issue of rapid efficacy waning while preserving the protective immune response against malaria sporozoites.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the amino acid sequence parameter by deleting the KQ motif (Lys-Gln dipeptide) from the PfCSP sequence. This parameter change in the antigen structure leads to sustained immune protection without the rapid efficacy loss observed with complete C-terminal domain-containing vaccines.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If complete PfCSP sequence including KQ motif is used, then initial immune response is generated, but sustained protection is not achieved

Engineering Contradiction:

Improveimmune response effectivenessVSAvoidprotection duration

Core Design Contradiction:

ReliabilityVSDuration of action of moving object

Solution Approach 1:

The patent extracts and removes the KQ motif from the PfCSP amino acid sequence to create an improved immunogen. This extraction of the problematic KQ motif eliminates the issue of rapid efficacy waning while preserving the protective immune response against malaria sporozoites.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the amino acid sequence parameter by deleting the KQ motif (Lys-Gln dipeptide) from the PfCSP sequence. This parameter change in the antigen structure leads to sustained immune protection without the rapid efficacy loss observed with complete C-terminal domain-containing vaccines.

Inventive Principle:

Principle #35Parameter changes

3Ease of manufacture

If traditional vaccine platforms are used, then vaccine production is achieved, but enhanced immunogenicity and sustained protection are not obtained

Engineering Contradiction:

Improvevaccine productionVSAvoidimmune response effectiveness

Core Design Contradiction:

Ease of manufactureVSReliability

Solution Approach 1:

The patent creates a composite immunogen by combining the modified PfCSP sequence (lacking KQ motif) with nanocage monomers such as ferritin. This composite structure enhances immunogenicity and elicits sustained protective immune responses while maintaining feasibility of production through recombinant expression systems.

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS20250242008A1Pfcsp-based immunogens and related composition and methods

Publication Date: 2025.07.31 MAX PLANCK GESELLSCHAFT ZUR FOERDERUNG DER WISSENSCHAFTEN EV

AI summary

Described herein is malarial immnunogen or a variant thereof comprising at least a portion of the wild-type PfCSP amino acid sequence lacking a KQ motif. In aspects, the malarial immunogen is lacking a KQP motif. For example, the immnunogens described herein, in aspects, exclude the C-terminal domain of PfCSP. In other aspects, the immunogens described herein specifically exclude a KQ or KQP motif. In aspects the immunogens described herein exclude an N-terminal KQ or KQP motif, which is part of the N-terminal junction region in PfCSP.