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Tumorvirus-specific Vaccination Strategies

Research Group Tumorvirus-specific Vaccination Strategies

apl. Prof. Dr. Martin Müller

Design of prophylactic vaccine antigen. Cross-neutralization epitopes of 8 different HPV types are inserted into a scaffold of thermostable thioredoxin. The antigen is forming heptamers due to the OVX313 domain.

PANHPVAX -Thermostable and broadly protective HPV vaccine
The N-terminal region of the human papillomavirus (HPV) L2 protein has been shown to contain epitopes able to induce the production of neutralizing and cross-neutralizing antibodies. Using bacterial thioredoxin as a scaffold, we managed to significantly enhance the immunogenicity of putative L2 neutralizing epitopes. In the past years, we extensively optimized the prophylactic vaccine antigen and also determined its safety in an animal model.

We now entered into a clinical development phase and are starting a phase I clinical trial (EudraCT No.: 2021-002584-22). This trial should demonstrate safety and immunogenicity. Our vaccine is based on a single molecule, is highly thermostable and more importantly, induces protective responses against all oncogenic HPV as well as a number of so called ‘low risk’ HPV. Therefore, the vaccine has the potential to provide protection against HPV also in regions where the current HPV vaccines cannot be distributed, which applies to about two thirds of all countries.

Jointly with the European Molecular Biology Laboratory (EMBL) in Heidelberg we have developed a standardized validated assay system which allows us the high-throughput detection of neutralizing antibodies against HPV16, HPV18, and other oncogenic HPV types (automated pseudovirion-based HPV-neutralization assay). This assay can be used for a multitude of epidemiological studies. In particular, the duration of the immunization-protection after the introduction of a new vaccine could be monitored with our assay in large study groups.


apl. Prof. Dr. Martin Müller
Tumorvirus-specific Vaccination Strategies (D335)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 242
69120 Heidelberg
Tel: +49 6221 42 4628

Selected Publications

  • A Broadly Protective Vaccine against Cutaneous Human Papillomaviruses. (2022). Filipe Mariz, Kathrin Balz, Manuela Dittrich, Yueru Zhang, Fan Yang, Xueer Zhao, Angelo Bolchi, Simone Ottonello, and Martin Müller. In press. A Broadly Protective Vaccine against Cutaneous Human Papillomaviruses. npj Vaccines, in press.
  • Sustainability of neutralising antibodies induced by bivalent or quadrivalent HPV vaccines and correlation with efficacy: a combined follow-up analysis of data from two randomised, double-blind, multicentre, phase 3 trials.(2021) Mariz FC, Gray P, Bender N, Eriksson T, Kann H, Apter D, Paavonen J, Pajunen E, Prager KM, Sehr P, Surcel HM, Waterboer T, Müller M, Pawlita M, Lehtinen M. Lancet Infect Dis. 2021 May 28:S1473-3099(20)30873-2. doi: 10.1016/S1473-3099(20)30873-2
  • Combined prophylactic and therapeutic immune responses against human papillomaviruses induced by a thioredoxin-based L2-E7 nanoparticle vaccine. Zhao X, Yang F, Mariz F, Osen W, Bolchi A, Ottonello S, Müller M. PLoS Pathog. 2020 Sep 4;16(9):e1008827. doi: 10.1371/journal.ppat.1008827. eCollection 2020 Sep.
  • Peak neutralizing and cross-neutralizing antibody 1 levels to human papillomavirus types 6/11/16/18/31/33/45/52/58 induced by bivalent and quadrivalent HPV vaccines (2019). Filipe Colaço Mariz, Noemi Bender, Devasena Anantharaman, Partha Basu, Neerja Bhatla, Madhavan Radhakrisna Pillai, Priya R Prabhu, Rengaswamy Sankaranarayanan Tiina Eriksson, Michael Pawlita, Kristina Prager, Peter Sehr, Tim Waterboer, Martin Müller, Matti Lehtinen. NPJ Vaccines. 2020 Feb 14;5:14. doi: 10.1038/s41541-020-0165-x. eCollection 2020.
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