Tumorvirus-specific Vaccination Strategies

Research Group Tumorvirus-specific Vaccination Strategies

apl. Prof. Dr. Martin Müller

Cells expressing HPV L1 and L2 capsid proteins (red and green labeled).
© dkfz.de

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 to study the host range of the papillomaviruses.
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. Before we can apply a thioredoxin L2 antigen in humans, we need to address cross-protective vaccine efficacy as well as safety issues e.g. in regard to thioredoxin scaffold. These issues are currently in the focus of our work.

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.
Another important question we are dealing with is the immune response against the viral capsid in the course of natural HPV infections. This includes to study the relevance of maternal antibodies in the infant.

Contact

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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