title: Cross-neutralization of antibodies induced by vaccination with Purified Chick Embryo Cell Vaccine (PCECV) against different Lyssavirus species.
abstract: BACKGROUND
  Rabies is a neglected zoonotic disease caused by viruses belonging to the genus lyssavirus. In endemic countries of Asia and Africa, where the majority of the estimated 60,000 human rabies deaths occur, it is mainly caused by the classical rabies virus (RABV) transmitted by dogs. Over the last decade new species within the genus lyssavirus have been identified. Meanwhile 15 (proposed or classified) species exist, including Australian bat lyssavirus (ABLV), European bat lyssavirus (EBLV-1 and -2), Duvenhage virus (DUVV), as well as Lagos bat virus (LBV) and Mokola virus (MOKV) and recently identified novel species like Bokeloh bat lyssavirus (BBLV), Ikoma bat lyssavirus (IKOV) or Lleida bat lyssavirus (LLBV). The majority of these lyssavirus species are found in bat reservoirs and some have caused human infection and deaths. Previous work has demonstrated that Purified Chick Embryo Cell Rabies Vaccine (PCECV) not only induces immune responses against classical RABV, but also elicits cross-neutralizing antibodies against ABLV, EBLV-1 and EBLV-2.
  
  
  METHODS
  Using the same serum samples as in our previous study, this study extension investigated cross-neutralizing activities of serum antibodies measured by rapid fluorescent focus inhibition test (RFFIT) against selected other non-classical lyssavirus species of interest, namely DUVV and BBLV, as well as MOKV and LBV.
  
  
  RESULTS
  Antibodies developed after vaccination with PCECV have neutralizing capability against BBLV and DUVV in the same range as against ABLV and EBLV-1 and -2. As expected, for the phylogenetically more distant species LBV no cross-neutralizing activity was found. Interestingly, 15 of 94 serum samples (16%) with a positive neutralizing antibody titer against RABV displayed specific cross-neutralizing activity (65-fold lower than against RABV) against one specific MOKV strain (Ethiopia isolate), which was not seen against a different strain (Nigeria isolate).
  
  
  CONCLUSIONS
  Cross-neutralizing activities partly correlate with the phylogenetic distance of the virus species. Cross-neutralizing activities against the species BBLV and DUVV of phylogroup 1 were demonstrated, in line with previous results of cross-neutralizing activities against ABLV and EBLV-1 and -2. Potential partial cross-neutralizing activities against more distant lyssavirus species like selected MOKV strains need further research.
authors.affiliation: a Novartis Vaccines; Medical Affairs ; Marburg , Germany.
authors.forename: Claudius
authors.initials: C
authors.lastname: Malerczyk
authors.forename: Conrad
authors.initials: C
authors.lastname: Freuling
authors.forename: Dieter
authors.initials: D
authors.lastname: Gniel
authors.forename: Alexandra
authors.initials: A
authors.lastname: Giesen
authors.forename: Thomas
authors.initials: T
authors.lastname: Selhorst
authors.forename: Thomas
authors.initials: T
authors.lastname: Müller
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D002642:Chick Embryo; D056738:Cross Protection / Q000276:immunology*; D004285:Dogs; D006801:Humans; D018114:Lyssavirus / Q000145:classification / Q000276:immunology*; D011818:Rabies / Q000276:immunology / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000276:immunology*; D014611:Vaccination
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D011819:Rabies Vaccines
keywords: PCECV; cross-neutralization; lyssavirus; rabies; vaccine