Tumorvirus-specific Vaccination Strategies

Yueru Zhang

The minor capsid protein L2 plays a critical role in virus assembly, infection, and replication. Although there have been some efforts to develop vaccines targeting the highly conserved immunogenic region within the L2 sequence, its structural properties remain largely unexplored. This lack of structural insight is primarily due to the inherent flexibility and instability of the full L2 protein. In this project, we aim to discover the structure of the immunogenic region of L2 by co-crystallizing it with corresponding neutralizing antibodies. By leveraging this structural and functional information, we hope to provide new perspectives on HPV vaccine development and optimization.

Predicted structure of HPV16 amino acids 1-45 was generated using AlphaFold 3. The immunogenic region is highlighted in the right panel. The structure is color-coded based on the prediction confidence (pLDDT): yellow indicates a pLDDT value between 50 and 70, light blue represents a pLDDT between 70 and 90, and blue indicates a pLDDT greater than 90.

Ecem Kaplan

HPV VLPs and capsomers have the potential to be used as a vaccine delivery platform due to their highly organized and repetitive structure. Due to its size, insertion of Trx-8mer epitope to surface exposed loops of L1 cannot be achieved without interfering with capsomer or VLP assembly. DogTag/DogCatcher was employed as a promising approach to decorate HPV 16 L1 capsomers or VLPs with L2 epitopes.  

Heiko Weyd

Key aspect of our vaccine concept are the broadly protective humoral responses induced by the L2-based polytope antigen PANHPVAX, currently evaluated in a clinical phase I study. We have demonstrated that vaccine-induced protection is driven by anti-L2 neutralizing antibodies. However, comprehension on memory B cell and innate immune responses induced by L2-based vaccines is poor. In this project, we follow-up on our prior observations by analyzing PANHPVAX-induced immunity with respect to L2-specific non-neutralizing antibodies and antibody profile as well as L2-specific Fc-effector functions, namely antibody-mediated cellular cytotoxicity and phagocytosis.