An mRNA Vaccine Encoding Rabies Virus Glycoprotein Induces Protection against Lethal Infection in Mice and Correlates of Protection in Adult and Newborn Pigs

PLoS Neglected Tropical Diseases

Volumn 10, Issue 6, 2016, Pages

  Schnee, Margit ^a   Vogel, Annette B ^b,c   Voss, Daniel ^a,d   Petsch, Benjamin ^a   Baumhof, Patrick ^a   Kramps, Thomas ^a,e   Stitz, Lothar ^b  

^a CureVac GmbH   (Germany)

^b FEDERAL RESEARCH INSTITUTE FOR ANIMAL HEALTH   (Germany)

^c BIONTECH AG   (Germany)

^d ROCHE INNOVATION CENTER MUNICH   (Germany)

^e BOEHRINGER INGELHEIM PHARMA GMBH AND CO KG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

NEUTRALIZING ANTIBODY; RABIES VACCINE; RABIES VIRUS GLYCOPROTEIN MESSENGER RNA; RNA VACCINE; UNCLASSIFIED DRUG; GLYCOPROTEIN; MESSENGER RNA; PEPTIDE FRAGMENT; RABIES VIRUS GLYCOPROTEIN PEPTIDE; RECOMBINANT VACCINE; VIRAL PROTEIN;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBODY TITER; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; ENZYME LINKED IMMUNOSPOT ASSAY; FEMALE; FLOW CYTOMETRY; HUMAN; HUMAN CELL; IMMUNIZATION; IMMUNOGENICITY; MOUSE; NEWBORN; NONHUMAN; PIG; PROTEIN EXPRESSION; RABIES; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SEROCONVERSION; VIRUS REPLICATION; ANIMAL; BAGG ALBINO MOUSE; C57BL MOUSE; CHEMISTRY; DOSE RESPONSE; GENETICS; HELA CELL LINE; IMMUNOLOGY; MORTALITY; NUCLEOTIDE SEQUENCE; PREGNANCY; SWINE DISEASES; T LYMPHOCYTE; VETERINARY;

ANIMALS; ANIMALS, NEWBORN; BASE SEQUENCE; DOSE-RESPONSE RELATIONSHIP, IMMUNOLOGIC; FEMALE; GLYCOPROTEINS; HELA CELLS; HUMANS; MICE; MICE, INBRED BALB C; MICE, INBRED C57BL; PEPTIDE FRAGMENTS; PREGNANCY; RABIES; RABIES VACCINES; RNA, MESSENGER; SWINE; SWINE DISEASES; T-LYMPHOCYTES; VACCINES, SYNTHETIC; VIRAL PROTEINS;

EID: 84978063234     PISSN: 19352727     EISSN: 19352735     Source Type: Journal    
DOI: 10.1371/journal.pntd.0004746     Document Type: Article

References (55)

1. Hemachudha T, Ugolini G, Wacharapluesadee S, Sungkarat W, Shuangshoti S, et al. (2013) Human rabies: neuropathogenesis, diagnosis, and management. Lancet Neurology12: 498–513. doi: 10.1016/S1474-4422(13)70038-323602163
2. Pathak S, Horton DL, Lucas S, Brown D, Quaderi S, et al. (2014) Diagnosis, management and post-mortem findings of a human case of rabies imported into the United Kingdom from India: a case report. Virology Journal11.
3. Ertl HCJ, (2009) Novel vaccines to human rabies. PLoS neglected tropical diseases3.
4. Wiktor TJ, György E, Schlumberger D, Sokol F, Koprowski H, (1973) Antigenic properties of rabies virus components. Journal of Immunology (Baltimore, Md: 1950)110: 269–276.
5. Cox JH, Dietzschold B, Schneider LG, (1977) Rabies virus glycoprotein. II. Biological and serological characterization. Infection and Immunity16: 754–759. 408269
6. Klingen Y, Conzelmann K-K, Finke S, (2008) Double-labeled rabies virus: live tracking of enveloped virus transport. Journal of Virology82: 237–245. 17928343
7. Meslin FX, Briggs DJ, (2013) Eliminating canine rabies, the principal source of human infection: what will it take?Antiviral Res98: 291–296. doi: 10.1016/j.antiviral.2013.03.01123523768
8. Condori-Condori RE, Streicker DG, Cabezas-Sanchez C, Velasco-Villa A, (2013) Enzootic and epizootic rabies associated with vampire bats, peru. Emerging Infectious Diseases19.
9. van Thiel P-PAM, de Bie RMA, Eftimov F, Tepaske R, Zaaijer HL, et al. (2009) Fatal human rabies due to Duvenhage virus from a bat in Kenya: failure of treatment with coma-induction, ketamine, and antiviral drugs. PLoS neglected tropical diseases3.
10. World Health O (2013) WHO Expert Consultation on Rabies. Second report. World Health Organization Technical Report Series: 1–139, back cover.
11. Rupprecht CE, Nagarajan T, Ertl H, (2016) Current Status and Development of Vaccines and Other Biologics for Human Rabies Prevention. Expert Rev Vaccines: 1–19.
12. Bourhy H, Goudal M, Mailles A, Sadkowska-Todys M, Dacheux L, et al. (2009) Is there a need for anti-rabies vaccine and immunoglobulins rationing in Europe?Euro Surveill14.
13. Amann R, Rohde J, Wulle U, Conlee D, Raue R, et al. (2013) A new rabies vaccine based on a recombinant ORF virus (parapoxvirus) expressing the rabies virus glycoprotein. Journal of Virology87: 1618–1630. doi: 10.1128/JVI.02470-1223175365
14. Hoerr I, Obst R, Rammensee HG, Jung G, (2000) In vivo application of RNA leads to induction of specific cytotoxic T lymphocytes and antibodies. Eur J Immunol30: 1–7. 10602021
15. Fotin-Mleczek M, Duchardt KM, Lorenz C, Pfeiffer R, Ojkic-Zrna S, et al. (2011) Messenger RNA-based vaccines with dual activity induce balanced TLR-7 dependent adaptive immune responses and provide antitumor activity. J Immunother34: 1–15. doi: 10.1097/CJI.0b013e3181f7dbe821150709
16. Solari EJ, Petscher Y, Folsom JS, (2012) Differentiating Literacy Growth of ELL Students With LD From Other High-Risk Subgroups and General Education Peers: Evidence From Grades 3–10. J Learn Disabil47: 329–348. doi: 10.1177/002221941246343523124380
17. Kallen K-J, Heidenreich R, Schnee M, Petsch B, Schlake T, (2013) A novel, disruptive vaccination technology: self-adjuvanted RNActive vaccines. Human Vaccines & Immunotherapeutics9: 2263–2276.
18. Kramps T, Probst J, (2013) Messenger RNA-based vaccines: progress, challenges, applications. Wiley interdisciplinary reviews RNA4: 737–749. doi: 10.1002/wrna.118923893949
19. Sahin U, Kariko K, Tureci O, (2014) mRNA-based therapeutics—developing a new class of drugs. Nat Rev Drug Discov13: 759–780. doi: 10.1038/nrd427825233993
20. Pascolo S, (2004) Messenger RNA-based vaccines. Expert Opin Biol Ther4: 1285–1294. 15268662
21. Pascolo S, (2015) The messenger's great message for vaccination. Expert Rev Vaccines14: 153–156. doi: 10.1586/14760584.2015.100087125586101
22. Carralot JP, Probst J, Hoerr I, Scheel B, Teufel R, et al. (2004) Polarization of immunity induced by direct injection of naked sequence-stabilized mRNA vaccines. Cellular and molecular life sciences: CMLS61: 2418–2424. 15378210
23. Scheel B, Teufel R, Probst J, Carralot J-P, Geginat J, et al. (2005) Toll-like receptor-dependent activation of several human blood cell types by protamine-condensed mRNA. European Journal of Immunology35: 1557–1566. 15832293
24. Schlake T, Thess A, Fotin-Mleczek M, Kallen K-J, (2012) Developing mRNA-vaccine technologies. RNA biology9: 1319–1330. doi: 10.4161/rna.2226923064118
25. Vardaxis NJ, Brans TA, Boon ME, Kreis RW, Marres LM, (1997) Confocal laser scanning microscopy of porcine skin: implications for human wound healing studies. J Anat190 (Pt 4): 601–611. 9183682
26. Sullivan TP, Eaglstein WH, Davis SC, Mertz P, (2001) The pig as a model for human wound healing. Wound Repair Regen9: 66–76. 11350644
27. WHO (2015) WHO Drug Information. http://appswhoint/medicinedocs/documents/s22000en/s22000enpdf 29: 242.
28. Pascolo S, (2006) Vaccination with messenger RNA. Methods Mol Med127: 23–40. 16988444
29. Pascolo S, (2008) Vaccination with messenger RNA (mRNA). Handb Exp Pharmacol: 221–235.
30. Cliquet F, Aubert M, Sagné L, (1998) Development of a fluorescent antibody virus neutralisation test (FAVN test) for the quantitation of rabies-neutralising antibody. Journal of Immunological Methods212: 79–87. 9671155
31. Cobbold SP, Jayasuriya A, Nash A, Prospero TD, Waldmann H, (1984) Therapy with monoclonal antibodies by elimination of T-cell subsets in vivo. Nature312: 548–551. 6150440
32. Reed LJMH, (1938) A simple method of estimation of fifty percent end points. Am J Hyg27: 493–497.
33. Hoffmann B, Freuling CM, Wakeley PR, Rasmussen TB, Leech S, et al. (2010) Improved safety for molecular diagnosis of classical rabies viruses by use of a TaqMan real-time reverse transcription-PCR "double check" strategy. J Clin Microbiol48: 3970–3978. doi: 10.1128/JCM.00612-1020739489
34. Petsch B, Schnee M, Vogel AB, Lange E, Hoffmann B, et al. (2012) Protective efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus infection. Nat Biotechnol30: 1210–1216. doi: 10.1038/nbt.243623159882
35. Watanabe H, Numata K, Ito T, Takagi K, Matsukawa A, (2004) Innate immune response in Th1- and Th2-dominant mouse strains. Shock22: 460–466. 15489639
36. Barth R, Gruschkau H, Bijok U, Hilfenhaus J, Hinz J, et al. (1984) A new inactivated tissue culture rabies vaccine for use in man. Evaluation of PCEC-vaccine by laboratory tests. Journal of Biological Standardization12: 29–46. 6199357
37. Saxena S, Dahiya SS, Sonwane AA, Patel CL, Saini M, et al. (2008) A sindbis virus replicon-based DNA vaccine encoding the rabies virus glycoprotein elicits immune responses and complete protection in mice from lethal challenge. Vaccine26: 6592–6601. doi: 10.1016/j.vaccine.2008.09.05518848857
38. Wiktor TJ, (1978) Cell-mediated immunity and postexposure protection from rabies by inactivated vaccines of tissue culture origin. Developments in Biological Standardization40: 255–264. 680397
39. Celis E, Karr RW, Dietzschold B, Wunner WH, Koprowski H, (1988) Genetic restriction and fine specificity of human T cell clones reactive with rabies virus. Journal of Immunology (Baltimore, Md: 1950)141: 2721–2728.
40. Meslin F.-X. KMM, Koprowski H, Laboratory Techniques in rabies. WHOGeneva1996Fourth Edition.
41. de Vries HE, Kuiper J, de Boer AG, Van Berkel TJ, Breimer DD, (1997) The blood-brain barrier in neuroinflammatory diseases. Pharmacological Reviews49: 143–155. 9228664
42. Phares TW, Kean RB, Mikheeva T, Hooper DC, (2006) Regional differences in blood-brain barrier permeability changes and inflammation in the apathogenic clearance of virus from the central nervous system. Journal of Immunology (Baltimore, Md: 1950)176: 7666–7675.
43. Solanki A, Radotra BD, Vasishta RK, (2009) Correlation of cytokine expression with rabies virus distribution in rabies encephalitis. Journal of Neuroimmunology217: 85–89. doi: 10.1016/j.jneuroim.2009.09.01919857907
44. Meurens F, Summerfield A, Nauwynck H, Saif L, Gerdts V, (2012) The pig: a model for human infectious diseases. Trends Microbiol20: 50–57. doi: 10.1016/j.tim.2011.11.00222153753
45. Mair KH, Sedlak C, Kaser T, Pasternak A, Levast B, et al. (2014) The porcine innate immune system: an update. Dev Comp Immunol45: 321–343. doi: 10.1016/j.dci.2014.03.02224709051
46. Jackson AC, (2013) Current and future approaches to the therapy of human rabies. Antiviral Research99: 61–67. doi: 10.1016/j.antiviral.2013.01.00323369672
47. Senior K, (2012) Global rabies elimination: are we stepping up to the challenge?The Lancet Infectious Diseases12: 366–367. 22690389
48. Tricou V, Bouscaillou J, Kamba Mebourou E, Koyanongo FD, Nakoune E, et al. (2016) Surveillance of Canine Rabies in the Central African Republic: Impact on Human Health and Molecular Epidemiology. PLoS Negl Trop Dis10: e0004433. doi: 10.1371/journal.pntd.000443326859829
49. Wunderli PS, Shaddock JH, Schmid DS, Miller TJ, Baer GM, (1991) The protective role of humoral neutralizing antibody in the NIH potency test for rabies vaccines. Vaccine9: 638–642. 1950097
50. Wunderli PS, Dreesen DW, Miller TJ, Baer GM, (2003) Effects of vaccine route and dosage on protection from rabies after intracerebral challenge in mice. American Journal of Veterinary Research64: 491–498. 12693542
51. Hooper DC, Phares TW, Fabis MJ, Roy A, (2009) The production of antibody by invading B cells is required for the clearance of rabies virus from the central nervous system. PLoS neglected tropical diseases3.
52. Kaur M, Rai A, Bhatnagar R, (2009) Rabies DNA vaccine: no impact of MHC class I and class II targeting sequences on immune response and protection against lethal challenge. Vaccine27: 2128–2137. doi: 10.1016/j.vaccine.2009.01.12819356616
53. Kaur M, Saxena A, Rai A, Bhatnagar R, (2010) Rabies DNA vaccine encoding lysosome-targeted glycoprotein supplemented with Emulsigen-D confers complete protection in preexposure and postexposure studies in BALB/c mice. FASEB J24: 173–183. doi: 10.1096/fj.09-13864419741168
54. Phares TW, Fabis MJ, Brimer CM, Kean RB, Hooper DC, (2007) A peroxynitrite-dependent pathway is responsible for blood-brain barrier permeability changes during a central nervous system inflammatory response: TNF-alpha is neither necessary nor sufficient. Journal of Immunology (Baltimore, Md: 1950)178: 7334–7343.
55. Stitz L, Vogel A, Schnee M, Voss D, Rauch S, et al. A thermostable messenger RNA based vaccine (manuscript in preparation).