Vaccine Technologies

The unit develops diagnostic assays and prevention strategies for infectious diseases, in human and veterinary medicine. A strong focus is on zoonoses and (re-)emerging viral infections. All state-of-the-art methods in virology, microbiology, molecular biology and immunology are well established, and the unit includes a BSL-3 laboratory with animal facility. Pathogens worked on in the lab include, among others, flaviviruses (West Nile virus, dengue virus, Zika virus), Influenza, PRRSV, and spore-forming bacteria. In addition, methods for the control of ectoparasites are being developed.

In order to inactivate pathogens for vaccines or other applications, we are developing a novel irradiation technology, together with three other Fraunhofer Institutes. Project partners include pharmaceutical and diagnostic companies as well as funding organizations such as the Bill and Melinda Gates Foundation.

The unit has know-how and technologies for the design and production of recombinant antigens from all kinds of viruses and microbes. Technologies include proprietary ways for the elimination of cross-reacting epitopes (e.g. in flavivirus diagnostic). These proteins are used for the development of serologic tests, e.g. ELISAs. Other diagnostics are PCRs (e.g. real time PCR) and virus culture.

Rockstroh A, Barzon L, Pacenti M, Palù G, Niedrig M, Ulbert S. Recombinant Envelope-Proteins with Mutations in the Conserved Fusion Loop Allow Specific Serological Diagnosis of Dengue-Infections. PLoS Negl Trop Dis. 2015 Nov 13;9(11):e0004218. DOI dx.doi.org/10.1371/journal.pntd.0004218. eCollection 2015.

The unit coordinates a consortium consisting of Fraunhofer IZI and three other Fraunhofer Institutes (FEP, IPA and IGB) for the development of low-energy electron irradiation (LEEI) for the generation of inactivated vaccines or novel diagnostic antigens.

Fertey J, Bayer L, Grunwald T, Pohl A, Beckmann J, Gotzmann G, Casado JP, Schönfelder J, Rögner FH, Wetzel C, Thoma M, Bailer SM, Hiller E, Rupp S, Ulbert S. Pathogens Inactivated by Low-Energy-Electron Irradiation Maintain Antigenic Properties and Induce Protective Immune Responses. Viruses 2016, 8(11), 319; DOI: dx.doi.org/10.3390/v8110319

Press releases

• Press release, November 3, 2016: New procedure for manufacturing safe and effective vaccines
• Press release, October 29, 2018: Pilot Plant for the Industrial-Scale Production of Safe and Effective Vaccines installed at the Fraunhofer Institute for Cell Therapy and Immunology (Fraunhofer IZI) in Leipzig
• Press release, Fraunhofer-Gesellschaft, January 3, 2019: Low-energy electron beams – Producing vaccines without the use of chemicals

A platform for the development and optimization of DNA vaccines was generated. These vaccines are applied using modern technologies, such as in vivo electroporation or nanoparticles.

Schneeweiss A, Chabierski S, Salomo M, Delaroque N, Al-Robaiy S, Grunwald T, Bürki K, Liebert UG, Ulbert S. A DNA vaccine encoding the E protein of West Nile virus is protective and can be boosted by recombinant domain DIII. Vaccine. 2011 Aug 26;29(37):6352-7. DOI dx.doi.org/10.1016/j.vaccine.2011.04.116. Epub 2011 May 17.

Protein-vaccines are used alone or in combination with DNA immunization (heterologous prime-boost strategies).

Verstrepen BE, Oostermeijer H, Fagrouch Z, van Heteren M, Niphuis H, Haaksma T, Kondova I, Bogers WM, de Filette M, Sanders N, Stertman L, Magnusson S, Lőrincz O, Lisziewicz J, Barzon L, Palù G, Diamond MS, Chabierski S, Ulbert S, Verschoor EJ. Vaccine-induced protection of rhesus macaques against plasma viremia after intradermal infection with a European lineage 1 strain of West Nile virus. PLoS One. 2014 Nov 13;9(11):e112568. DOI dx.doi.org/10.1371/journal.pone.0112568. eCollection 2014.

• AJ Roboscreen GmbH
• Biomedical Primate Research Centre
• Fraunhofer Institute for Elec­tron Beam and Plasma Technology FEP
• Fraunhofer Institute for Interfacial Engineering and Biotechnology IGB
• Fraunhofer Institute for Manufacturing Engineering and Automation IPA
• Fraunhofer Institute for Molecular Biology and Applied Ecology IME
• Ghent University, Faculty of Veterinary Medicine
• Novavax AB
  
• University of Leipzig, Faculty of Medicine
• University of Leipzig, Faculty of Veterinary Medicine
• University of Padova, Faculty of Medicine and Surgery
• University of Thessaloniki, Medical School
• University of Zürich
• Washington University School of Medicine, Department of Medicine, Division of Infectious Diseases

• Rockstroh A, Barzon L, Kumbukgolla W, Su HX, Lizarazo E, Vincenti-Gonzalez MF, Tami A, Ornelas AMM, Aguiar RS, Cadar D, Schmidt-Chanasit J, Ulbert S. Dengue Virus IgM Serotyping by ELISA with Recombinant Mutant Envelope Proteins. Emerg Infect Dis. 2019 Jan 17;25(1). dx.doi.org/10.3201/eid2501.180605.
• Bayer L, Fertey J, Ulbert S, Grunwald T. Immunization with an adjuvanted low-energy electron irradiation inactivated respiratory syncytial virus vaccine shows immunoprotective activity in mice. Vaccine. 2018 Mar 14;36(12):1561-1569. dx.doi.org/10.1016/j.vaccine.2018.02.014
• Rockstroh A, Moges B, Barzon L, Sinigaglia A, Palù G, Kumbukgolla W, Schmidt-Chanasit J, Sarno M, Brites C, Moreira-Soto A, Drexler JF, Ferreira OC, Ulbert S. Specific detection of dengue and Zika virus antibodies using envelope proteins with mutations in the conserved fusion loop. Emerg Microbes Infect. 2017 Nov 8;6(11):e99. dx.doi.org/10.1038/emi.2017.87.
• Netto EM, Moreira-Soto A, Pedroso C, Höser C, Funk S, Kucharski AJ, Rockstroh A, Kümmerer BM, Sampaio GS, Luz E, Vaz SN, Dias JP, Bastos FA, Cabral R, Kistemann T, Ulbert S, de Lamballerie X, Jaenisch T, Brady OJ, Drosten C, Sarno M, Brites C, Drexler JF. High Zika Virus Seroprevalence in Salvador, Northeastern Brazil Limits the Potential for Further Outbreaks. MBio. 2017 Nov 14;8(6). pii: e01390-17. dx.doi.org/10.1128/mBio.01390-17.
• Rockstroh A, Moges B, Barzon L, Sinigaglia A, Palù G, Kumbukgolla W, Schmidt-Chanasit J, Sarno M, Brites C, Moreira-Soto A, Drexler JF, Ferreira OC, Ulbert S. Specific detection of dengue and Zika virus antibodies using envelope proteins with mutations in the conserved fusion loop. Emerg Microbes Infect. 2017 Nov 8;6(11):e99. dx.doi.org/10.1038/emi.2017.87.
• Fertey J, Bayer L, Grunwald T, Pohl A, Beckmann J, Gotzmann G, Casado JP, Schönfelder J, Rögner FH, Wetzel C, Thoma M, Bailer SM, Hiller E, Rupp S, Ulbert S. Pathogens Inactivated by Low-Energy-Electron Irradiation Maintain Antigenic Properties and Induce Protective Immune Responses. Viruses. 2016 Nov 23;8(11). pii: E319.
• Makert GR, Vorbrüggen S, Krautwald-Junghanns ME, Voss M, Sohn K, Buschmann T, Ulbert S. A method to identify protein antigens of Dermanyssus gallinae for the protection of birds from poultry mites. Parasitol Res. 2016 Jul;115(7):2705-13. DOI dx.doi.org/10.1007/s00436-016-5017-2
• Fischer D, Angenvoort J, Ziegler U, Fast C, Maier K, Chabierski S, Eiden M, Ulbert S, Groschup MH, Lierz M. DNA vaccines encoding the envelope protein of West Nile virus lineages 1 or 2 administered intramuscularly, via electroporation and with recombinant virus protein induce partial protection in large falcons (Falco spp.). Vet Res. 2015 Aug 17;46(1):87. DOI dx.doi.org/10.1186/s13567-015-0220-1.
• Rockstroh A, Barzon L, Pacenti M, Palù G, Niedrig M, Ulbert S. Recombinant Envelope-Proteins with Mutations in the Conserved Fusion Loop Allow Specific Serological Diagnosis of Dengue-Infections. PLoS Negl Trop Dis. 2015 Nov 13;9(11):e0004218. DOI dx.doi.org/10.1371/journal.pntd.0004218
• Barzon L, Pacenti M, Franchin E, Squarzon L, Sinigaglia A, Ulbert S, Cusinato R, Palù G. Isolation of West Nile virus from urine samples of patients with acute infection. Journal of Clinical Microbiology. 2014 Sep;52(9):3411-3. DOI dx.doi.org/10.1128/JCM.01328-14.
• Chabierski S, Barzon L, Papa A, Niedrig M, Bramson JL, Richner JM, Palù G, Diamond MS, Ulbert S. Distinguishing West Nile virus infection using a recombinant envelope protein with mutations in the conserved fusion-loop. BMC Infectious Diseases. 2014 May 9;14:246. DOI dx.doi.org/10.1186/1471-2334-14-246.
• De Filette M, Chabierski S, Andries O, Ulbert S, Sanders NN. T cell epitope mapping of the e-protein of west nile virus in BALB/c mice. PLoS One. 2014 Dec 15;9(12):e115343.DOI: dx.doi.org/10.1371/journal.pone.0115343.
• De Filette M, Soehle S, Ulbert S, Richner J, Diamond MS, Sinigaglia A, Barzon L, Roels S, Lisziewicz J, Lörincz O, Sanders NN.  Vaccination of mice using the West Nile virus E-protein in a DNA prime-protein boost strategy stimulates cell-mediated immunity and protects mice against a lethal challenge. PLoS One. 2014 Feb 4;9(2):e87837.DOI: dx.doi.org/10.1371/journal.pone.0087837.
• Friedrich S, Schmidt T, Geissler R, Lilie H, Chabierski S, Ulbert S, Liebert UG, Golbik RP, Behrens SE. AUF1 p45 promotes West Nile virus replication by an RNA chaperone activity that supports cyclization of the viral genome. Journal of Virology. 2014 Oct;88(19):11586-99.DOI: dx.doi.org/10.1128/JVI.01283-14.
• Magnusson SE, Karlsson KH, Reimer JM, Corbach-Söhle S, Patel S, Richner JM, Nowotny N, Barzon L, Bengtsson KL, Ulbert S, Diamond MS, Stertman L. Matrix-M™ adjuvanted envelope protein vaccine protects against lethal lineage 1 and 2 West Nile virus infection in mice. Vaccine. 2014 Feb 7;32(7):800-8. DOI dx.doi.org/10.1016/j.vaccine.2013.12.030.
• Ulbert S, Magnusson SE. Technologies for the development of West Nile virus vaccines. Future Microbiology. 2014;9(10):121-32. DOI dx.doi.org/10.2217/fmb.14.67.
• Verstrepen BE, Fagrouch Z, van Heteren M, Buitendijk H, Haaksma T, Beenhakker N, Palù G, Richner JM, Diamond MS, Bogers WM, Barzon L, Chabierski S, Ulbert S, Kondova I, Verschoor EJ. Experimental infection of rhesus macaques and common marmosets with a European strain of West Nile virus. PLoS Neglected Tropical Diseases. 2014 Apr 17;8(4):e2797. DOI dx.doi.org/10.1371/journal.pntd.0002797.
• Verstrepen BE, Oostermeijer H, Fagrouch Z, Van Heteren M, Niphuis H, Haaksma T, Kondova I, Bogers WM, De Filette M, Sanders N, Stertman L, Magnusson S, Lörincz O, Lisziewicz J, Barzon L, Palù G, Diamond MS, Chabierski S, Ulbert S, Verschoor E.J. Vaccine-induced protection of rhesus macaques against plasma viremia after intradermal infection with a European lineage 1 strain of West Nile virus. PLoS One, 9 (2014), e112568. DOI dx.doi.org/10.1371/journal.pone.0112568
• Chabierski S, Makert GR, Kerzhner A, Barzon L, Fiebig P, Liebert UG, Papa A, Richner JM, Niedrig M, Diamond MS, Palù G, Ulbert S.  Antibody responses in humans infected with newly emerging strains of West Nile Virus in Europe. 2013, PLoS ONE, 8(6), e66507.
• De Filette MC, Ulbert S, Diamond M, Sanders NN. Recent progress in West Nile virus diagnosis and vaccination. Vet Res.43 (2012), 1, S. 16. doi: 10.1186/1297-9716-43-16.
• Schneeweiss A, Chabierski S, Salomo M, Delaroque N, Al-Robaiy S, Grunwald T, Bürki K, Liebert UG, Ulbert S. A DNA vaccine encoding the E protein of West Nile Virus is protective and can be boosted by recombinant domain DIII. Vaccine, 29 (2011), S. 6352-6357.
• Ulbert S. West Nile Virus: The Complex Biology of an Emerging Pathogen. Intervirology, 54 (2011), S. 171-184.
• Schneeweiss A, Buyens K, Giese M, Sanders N, Ulbert S. Synergistic effects between natural histone mixtures and polyethylenimine in non-viral gene delivery in vitro. Int J Pharm. 400 (2010), 1-2, S. 86-95.
• Heinrich A, Riethmüller D, Gloger M, Schusser GF, Giese M, Ulbert S. RNA interference protects horse cells in vitro from infection with Equine Arteritis Virus. Antivir Res, 81 (2009), 3, S. 209-216.