Re-engineering nano particle HPV prophylactic vaccine based on minor capsid protein L2

Fan Yang, PhD student

Introduction

This image compares the molecular structures of Thioredoxin (left) and Thioredoxin-L2 (right). Key differences are illustrated, highlighting changes in specific sections depicted in pink and blue. An arrow indicates the transition from Thioredoxin to Thioredoxin-L2, emphasizing structural modifications. — predicted surface exposure of the HPV L2-peptides on thioredoxin | © dkfz.de

The N-terminus of the HPV minor capsid protein L2 contains several epitopes which are able to elicit neutralizing antibodies with the ability of cross protect against different types of HPVs. In order to improve the immunogenicity of L2 based vaccine, we employed the Pyrococcus furiosus thioredoxin (PfTrx) as platform.

Alternative text: "Two electron microscopy images showing nanoparticles. The left image displays a dense array of encapsulin-trx-HPV16 L2 *3 antigens, while the right image depicts trx-HPV16 L2 *3-pf. ferritin with distinct structures. Both illustrate results related to nanoparticle antigens." — Electron micrographs of nanoparticles produced in insect cells © dkfz.de

Diagram illustrating the structures of nanoparticle (NP) antigens derived from Pf. Encasulin and Pf. Ferritin. Multiple configurations are shown, highlighting various combinations of proteins and ferritin constructs. The chart includes color-coded boxes representing different antigen types and their respective structures. — © dkfz.de

The immunogenic activity of NP-associated antigens was improved compared to free individual antigens because NPs can deliver many antigens owing to their enhanced surface to volume ratio and are easily taken up by DCs. The objective of this project is to determine whether the immunogenicity of Trx-L2 antigens can be further improved by their presentation on nanoparticles (NP) such as encapsulin and ferritin. We synthesize the antigens which the L2 epitopes of HPVs display on the nanoparticle surface in order to improve the immunogenicity.