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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.

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. Currently, a GMP-conform production process is being developed and a phase I clinical trial is scheduled for end of 2019/beginning of 2020. 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.

Besides the development of papillomavirus vaccine strategies we are interested to study the functions of the structural proteins L1 and L2 in the course of the viral life cycle. With the help of VLPs we are able to investigate interactions of the viruses with the cells at early steps of infection. The L2 protein plays a central role in the packaging of the viral genome into the capsids. By packaging heterologous DNA into capsids we are able to produce so called pseudovirions. With these we can detect virus-neutralizing antibodies in the sera of immunized animals but also in human sera. In addition, pseudovirions allow studying the host range of the papillomaviruses.

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 (F035)
Deutsches Krebsforschungszentrum
Im Neuenheimer Feld 242
69120 Heidelberg
Tel: +49 6221 42 4628

Selected Publications

  • Christina Hölscher, Florian Sonntag, Katharina Henrich, Qingxin Chen, Jürgen Beneke, Petr Matula, Karl Rohr, Lars Kaderali, Nina Beil, Holger Erfle, Jürgen A. Kleinschmidt, and Martin Müller (2015) The SUMOylation pathway restricts gene transduction by adeno-associated viruses Plos. Pathogens 1;11(12): e1005281
  • Hanna Seitz, Lis Ribeiro-Müller, Elena Canali, Angelo Bolchi,Massimo Tommasino, Simone Ottonello,Martin Müller. (2015) Robust in vitro and in vivo neutralization against multiple high-risk HPV types induced by a thermostable thioredoxin-L2 vaccine. Cancer Prev Res (Phila). Jul 13. pii: canprevres.0164.2015
  • John Schiller and Martin Müller. (2015). The Next Generation of HPV Vaccines. Lancet Oncology, 16: e217-225
  • Hanna Seitz, Elena Canali, Lis Ribeiro-Müller, Anikó Palfi, Angelo Bolchi, Massimo Tommasino, Simone Ottonello, Martin Müller (2014) A three component mix of thioredoxin-L2 antigens elicits broadly neutralizing responses against oncogenic human papillomaviruses. Vaccine, 7:2610-2617
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