Transient Facial Nerve Paralysis (Bell's Palsy) following Intranasal Delivery of a Genetically Detoxified Mutant of Escherichia coli Heat Labile Toxin

• Published in: PloS one Vol. 4; no. 9; p. e6999
• Main Authors: Lewis, David J. M., Huo, Zhiming, Barnett, Susan, Kromann, Ingrid, Giemza, Rafaela, Galiza, Eva, Woodrow, Maria, Thierry-Carstensen, Birgit, Andersen, Peter, Novicki, Deborah, Del Giudice, Giuseppe, Rappuoli, Rino
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.09.2009; Public Library of Science (PLoS)
• Subjects: Adjuvants; Adult; AIDS Vaccines - adverse effects; Antigens; Axonal transport; Axons - metabolism; Bacterial Toxins - genetics; Bell Palsy - etiology; Bell's palsy; Bells palsy; Binding; Cholera; Clinical trials; Compression; Cytomegalovirus; E coli; Eardrum; Enterotoxins - genetics; Escherichia coli; Escherichia coli - metabolism; Escherichia coli Proteins - genetics; Facial nerve; Female; Gangliosides - chemistry; Glycoproteins; HIV; Human immunodeficiency virus; Humans; Immune response; Immune system; Immunoglobulins; Infectious Diseases/HIV Infection and AIDS; Infectious Diseases/Respiratory Infections; Inflammation; Inflammatory diseases; Influenza; Influenza vaccines; Intranasal administration; Male; Medical research; Migraine; Mucosa; Mutation; Mycobacterium bovis; Mycobacterium tuberculosis; Paralysis; Protein Binding; Proteins; Tetanus; Toxins; Tuberculosis; Tuberculosis Vaccines - adverse effects; Vaccines; Vaccines, Inactivated - adverse effects; Virology/Vaccines; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0006999

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 The individual component(s) responsible for paralysis were not identified, and the vaccine was withdrawn. 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. 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.