Preclinical Validation

The center for animal experimentation is a preclinical development hub within the Fraunhofer IZI network. Our qualified members of staff, who are particularly experienced in the hygienic management of animals, have access to modern facilities which fulfil the highest standards in animal husbandry. At the same time, different pharmacological and pharmacokinetic issues are processed and discussed by the unit, both in vitro and in vivo. The potentialities of work involving organisms range here from biological safety level 1 through to safety level 3 in accordance with the genetic engineering law / ordinance on biological agents.

The unit develops and investigates drug and vaccine candidates in cell culture experiments and various trials involving animal experiments, optionally under GLP standards. This research is focused in part on the development and efficacy testing of innovative vaccines for humans and animals.

Development of a vaccine against Respiratory Syncytial Virus

Human respiratory syncytial virus (RSV) usually only leads to mild complaints such as cold, cough or hoarseness. However, this virus is the greatest infectiological issue affecting premature babies and babies younger than six months old. The virus exhibits a severe disease progression among these infants which often has to be treated in hospital. At present, there is neither a therapy nor a vaccine which effectively protects against the RSV infection. A test among children in the 1960s involving a chemically inactive vaccination had a contrary effect: The RSV infection was seen to strengthen when contracted naturally.

Genetic vaccines are currently being tested to be developed for a series of indications. An innovative vaccination method was investigated with the aid of genetic vaccines as part of a major study. This involved a circular DNA molecule being administered as a vaccine, followed by a pain-free vaccination sprayed into the throat. This combination of vaccinations demonstrated surprisingly complete protection against infection with the virus. These promising, preclinical successes are now to be further tested in humans and expanded to other vaccine candidates.

  • Helmholtz Centre for Environmental Research – UFZ
  • Ichor Medical Systems
  • InstrAction GmbH
  • Pilot Pflanzenöltechnologie Magdeburg e.V.
  • University of Leipzig, Faculty of Veterinary Medicine, Institute for Virology

  • Grunwald T, Ulbert S. Improvement of DNA vaccination by adjuvants and sophisticated delivery devices: vaccine-platforms for the battle against infectious diseases. Clin Exp Vaccine Res. 2015 Jan;4(1):1-10. DOI http://dx.doi.org/10.7774/cevr.2015.4.1.1
  • Faissner S, Ambrosius B, Schanzmann K, Grewe B, Potthoff A, Münch J, Sure U, Gramberg T, Wittmann S, Brockmeyer N, Uberla K, Gold R, Grunwald T, Chan A. Cytoplasmic HIV-RNA in monocytes determines microglial activation and neuronal cell death in HIV-associated neurodegeneration. Exp Neurol. 2014 Nov;261:685-97. DOI http://dx.doi.org/10.1016/j.expneurol.2014.08.011
  • Grunwald T, Tenbusch M, Schulte R, Raue K, Wolf H, Hannaman D, de Swart RL, Uberla K, Stahl-Hennig C. Novel vaccine regimen elicits strong airway immune responses and control of respiratory syncytial virus in nonhuman primates. J Virol. 2014 Apr;88(8):3997-4007. DOI http://dx.doi.org/10.1128/JVI.02736-13
  • Sharma A, Wendland R, Sung B, Wu W, Grunwald T, Worgall S. Maternal immunization with chimpanzee adenovirus expressing RSV fusion protein protects against neonatal RSV pulmonary infection. Vaccine. 2014 Sep 29;32(43):5761-8. DOI http://dx.doi.org/10.1016/j.vaccine.2014.08.049
  • Lai D, Odimegwu DC, Esimone C, Grunwald T, Proksch P. Phenolic compounds with in vitro activity against respiratory syncytial virus from the Nigerian lichen Ramalina farinacea. Planta Med. 2013 Oct;79(15):1440-6. DOI http://dx.doi.org/10.1055/s-0033-1350711
  • Pachernegg S, Joshi I, Muth-Köhne E, Pahl S, Münster Y, Terhag J, Karus M, Werner M, Ma-Högemeier ZL, Körber C, Grunwald T, Faissner A, Wiese S, Hollmann M. Undifferentiated embryonic stem cells express ionotropic glutamate receptor mRNAs. Front Cell Neurosci. 2013 Dec 3;7:241. DOI http://dx.doi.org/10.3389/fncel.2013.00241
  • Stab V, Nitsche S, Niezold T, Storcksdieck Genannt Bonsmann M, Wiechers A, Tippler B, Hannaman D, Ehrhardt C, Uberla K, Grunwald T, Tenbusch M. Protective efficacy and immunogenicity of a combinatory DNA vaccine against Influenza A Virus and the Respiratory Syncytial Virus. PLoS One. 2013 Aug 14;8(8):e72217. DOI http://dx.doi.org/10.1371/journal.pone.0072217
  • Décard BF, von Ahsen N, Grunwald T, Streit F, Stroet A, Niggemeier P, Schottstedt V, Riggert J, Gold R, Chan A. Low vitamin D and elevated immunoreactivity against Epstein-Barr virus before first clinical manifestation of multiple sclerosis. J Neurol Neurosurg Psychiatry. 2012 Dec;83(12):1170-3. DOI http://dx.doi.org/10.1136/jnnp-2012-303068
  • Grewe B, Hoffmann B, Ohs I, Blissenbach M, Brandt S, Tippler B, Grunwald T, Uberla K. Cytoplasmic utilization of human immunodeficiency virus type 1 genomic RNA is not dependent on a nuclear interaction with gag. J Virol. 2012 Mar;86(6):2990-3002. DOI http://dx.doi.org/10.1128/JVI.06874-11
  • 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 http://dx.doi.org/10.1016/j.vaccine.2011.04.116
  • Tenbusch M, Grunwald T, Niezold T, Storcksdieck Genannt Bonsmann M, Hannaman D, Norley S, Uberla K. Codon-optimization of the hemagglutinin gene from the novel swine origin H1N1 influenza virus has differential effects on CD4(+) T-cell responses and immune effector mechanisms following DNA electroporation in mice. Vaccine. 2010 Apr 26;28(19):3273-7. DOI http://dx.doi.org/10.1016/j.vaccine.2010.02.090
  • Esimone CO, Grunwald T, Nworu CS, Kuate S, Proksch P, Uberla K. Broad spectrum antiviral fractions from the lichen Ramalina farinacea (L.) Ach. Chemotherapy. 2009;55(2):119-26. DOI http://dx.doi.org/10.1159/000194974
  • Kohlmann R, Schwannecke S, Tippler B, Ternette N, Temchura VV, Tenbusch M, Uberla K, Grunwald T. Protective efficacy and immunogenicity of an adenoviral vector vaccine encoding the codon-optimized F protein of respiratory syncytial virus. J Virol. 2009 Dec;83(23):12601-10. DOI http://dx.doi.org/10.1128/JVI.01036-09
  • Potthoff A, Schwannecke S, Nabi G, Hoffmann D, Grunwald T, Wildner O, Brockmeyer NH, Uberla K, Tenbusch M. Immunogenicity and efficacy of intradermal tattoo immunization with adenoviral vector vaccines. Vaccine. 2009 May 11;27(21):2768-74. DOI http://dx.doi.org/10.1016/j.vaccine.2009.03.001
  • Röhrs S, Kutzner N, Vlad A, Grunwald T, Ziegler S, Müller O. Chronological expression of Wnt target genes Ccnd1, Myc, Cdkn1a, Tfrc, Plf1 and Ramp3. Cell Biol Int. 2009 Apr;33(4):501-8. DOI http://dx.doi.org/10.1016/j.cellbi.2009.01.016
  • Stang A, Petrasch-Parwez E, Brandt S, Dermietzel R, Meyer HE, Stühler K, Liffers ST, Uberla K, Grunwald T. Unintended spread of a biosafety level 2 recombinant retrovirus. Retrovirology. 2009 Sep 22;6:86. DOI http://dx.doi.org/10.1186/1742-4690-6-86
  • Eckardt-Michel J, Lorek M, Baxmann D, Grunwald T, Keil GM, Zimmer G. The fusion protein of respiratory syncytial virus triggers p53-dependent apoptosis. J Virol. 2008 Apr;82(7):3236-49. DOI http://dx.doi.org/10.1128/JVI.01887-07
  • Esimone CO, Eck G, Duong TN, Uberla K, Proksch P, Grunwald T. Potential anti-respiratory syncytial virus lead compounds from Aglaia species. Pharmazie. 2008 Oct;63(10):768-73.
  • Brandt S, Blissenbach M, Grewe B, Konietzny R, Grunwald T, Uberla K. Rev proteins of human and simian immunodeficiency virus enhance RNA encapsidation. PLoS Pathog. 2007 Apr;3(4):e54.
  • Neuhoff S, Moers J, Rieks M, Grunwald T, Jensen A, Dermietzel R, Meier C. Proliferation, differentiation, and cytokine secretion of human umbilical cord blood-derived mononuclear cells in vitro. Exp Hematol. 2007 Jul;35(7):1119-31.
  • Ternette N, Stefanou D, Kuate S, Uberla K, Grunwald T. Expression of RNA virus proteins by RNA polymerase II dependent expression plasmids is hindered at multiple steps. Virol J. 2007 Jun 5;4:51.
  • Ternette N, Tippler B, Uberla K, Grunwald T. Immunogenicity and efficacy of codon optimized DNA vaccines encoding the F-protein of respiratory syncytial virus. Vaccine. 2007 Oct 10;25(41):7271-9.
  • Brandt S, Grunwald T, Lucke S, Stang A, Uberla K. Functional replacement of the R region of simian immunodeficiency virus-based vectors by heterologous elements. J Gen Virol. 2006 Aug;87(Pt 8):2297-307.
  • Jogler C, Hoffmann D, Theegarten D, Grunwald T, Uberla K, Wildner O. Replication properties of human adenovirus in vivo and in cultures of primary cells from different animal species. J Virol. 2006 Apr;80(7):3549-58.
  • Quack I, Rump LC, Gerke P, Walther I, Vinke T, Vonend O, Grunwald T, Sellin L. beta-Arrestin2 mediates nephrin endocytosis and impairs slit diaphragm integrity. Proc Natl Acad Sci U S A. 2006 Sep 19;103(38):14110-5.
  • Esimone CO, Grunwald T, Wildner O, Nchinda G, Tippler B, Proksch P, Uberla K. In vitro pharmacodynamic evaluation of antiviral medicinal plants using a vector-based assay technique. J Appl Microbiol. 2005;99(6):1346-55.
  • Lucke S, Grunwald T, Uberla K. Reduced mobilization of Rev-responsive element-deficient lentiviral vectors. J Virol. 2005 Jul;79(14):9359-62.
  • Grunwald T, Pedersen FS, Wagner R, Uberla K. Reducing mobilization of simian immunodeficiency virus based vectors by primer complementation. J Gene Med. 2004 Feb;6(2):147-54.