title: Transient facial nerve paralysis (Bell's palsy) following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin.
abstract: BACKGROUND
  An association was previously established between facial nerve paralysis (Bell's palsy) and intranasal administration of an inactivated influenza virosome vaccine containing an enzymatically active Escherichia coli Heat Labile Toxin (LT) adjuvant. The individual component(s) responsible for paralysis were not identified, and the vaccine was withdrawn.
  
  
  RESULTS
  Subjects participating in two contemporaneous non-randomized Phase 1 clinical trials of nasal subunit vaccines against Human Immunodeficiency Virus and tuberculosis, both of which employed an enzymatically inactive non-toxic mutant LT adjuvant (LTK63), underwent active follow-up for adverse events using diary-cards and clinical examination. Two healthy subjects experienced transient peripheral facial nerve palsies 44 and 60 days after passive nasal instillation of LTK63, possibly a result of retrograde axonal transport after neuronal ganglioside binding or an inflammatory immune response, but without exaggerated immune responses to LTK63.
  
  
  CONCLUSIONS
  While the unique anatomical predisposition of the facial nerve to compression suggests nasal delivery of neuronal-binding LT-derived adjuvants is inadvisable, their continued investigation as topical or mucosal adjuvants and antigens appears warranted on the basis of longstanding safety via oral, percutaneous, and other mucosal routes.
authors.affiliation: St George's Vaccine Institute, St George's University of London, London, United Kingdom. d.lewis@sgul.ac.uk
authors.forename: David J M
authors.initials: DJ
authors.lastname: Lewis
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Huo
authors.forename: Susan
authors.initials: S
authors.lastname: Barnett
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kromann
authors.forename: Rafaela
authors.initials: R
authors.lastname: Giemza
authors.forename: Eva
authors.initials: E
authors.lastname: Galiza
authors.forename: Maria
authors.initials: M
authors.lastname: Woodrow
authors.forename: Birgit
authors.initials: B
authors.lastname: Thierry-Carstensen
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.forename: Deborah
authors.initials: D
authors.lastname: Novicki
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects*; D000328:Adult; D001369:Axons / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics*; D020330:Bell Palsy / Q000209:etiology*; D004768:Enterotoxins / Q000235:genetics*; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics*; D005260:Female; D005732:Gangliosides / Q000737:chemistry; D006801:Humans; D007249:Inflammation; D008297:Male; D009154:Mutation; D011485:Protein Binding; D032581:Tuberculosis Vaccines / Q000009:adverse effects*; D015164:Vaccines, Inactivated / Q000009:adverse effects*
chemical_list: D016915:AIDS Vaccines; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D005732:Gangliosides; D032581:Tuberculosis Vaccines; D015164:Vaccines, Inactivated; C027538:heat-labile enterotoxin, E coli