Rationally Designed Modular Helical-Bundle Rocket-Model Protein Nanorod and Its Application Exploration as a Multi-Antigen Vaccine Platform

This study discovered that a rationally designed polypeptide rich in repetitive sequences can spontaneously fold and assemble into a class of highly ordered protein nanorods. The structure is formed by the linear linkage of multiple helical structural units, exhibiting a uniform, rigid rod-like morphology in both molecular simulations and experimental characterizations. It is defined in this research as the Modular Helical-bundle Rocket-model Protein (MHRP). Although MHRP lacks the hydrolytic enzyme activity originally intended, its structure demonstrates remarkable programmability and modularity: by genetically fusing different viral antigenic epitopes at specific sites within its repetitive units, various epitopes can be precisely and densely displayed on the nanorod surface, thereby constructing a novel multi-antigen presentation platform (MHRP-MAP). In vitro experiments show that the recombinant protein can be stably expressed while maintaining structural integrity. Preliminary cellular experiments indicate that MHRP-MAP can be effectively internalized by antigen-presenting cells and activate adaptive immune responses. This study confirms the feasibility of repurposing unexpected structural outcomes from rational design into functional biomaterials. As a well-ordered nanovaccine carrier with controllable antigen arrangement, MHRP-MAP offers a new strategy for developing efficient and broad-spectrum synthetic vaccines, while also providing a research paradigm of "structure-function" repurposing in the field of de novo protein design.