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Clinical Trial
. 2009 Sep 16;4(9):e6999.
doi: 10.1371/journal.pone.0006999.

Transient facial nerve paralysis (Bell's palsy) following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin

David J M Lewis  1 , Zhiming Huo, Susan Barnett, Ingrid Kromann, Rafaela Giemza, Eva Galiza, Maria Woodrow, Birgit Thierry-Carstensen, Peter Andersen, Deborah Novicki, Giuseppe Del Giudice, Rino Rappuoli
Affiliations
Clinical Trial

Transient facial nerve paralysis (Bell's palsy) following intranasal delivery of a genetically detoxified mutant of Escherichia coli heat labile toxin

David J M Lewis et al. PLoS One. .

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 The individual component(s) responsible for paralysis were not identified, and the vaccine was withdrawn.

Methodology/principal findings: 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/significance: 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.

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Conflict of interest statement

Competing Interests: David J.M. Lewis, Zhiming Huo, Rafaela Giemza, Maria Woodrow and Eva Galiza are employees of St George's - University of London which co-sponsored trial 2005-005140-81. Susan Barnett, Deborah Novicki, Giuseppe Del Giudice and Rino Rappuoli are employees of Novartis Vaccines which has intellectual property rights on LTK63, and co-sponsored trial 2005-005140-81. Ingrid Kromann, Birgit Thierry-Carstensen and Peter Andersen are employees of Staten Serum Institute which has intellectual property rights on Ag85-ESAT6, and sponsored trial 2005-005983-10.

Figures

Figure 1
Figure 1. Serum and nasal lavage antibody response to LTK63.
Anti-LTK63 specific IgG and IgA in serum (µg/mL, (A)) and nasal lavage (ng/mL, (B)) measured by ELISA. Time course for individual response of Case 1 (left figures) and Case 2 (right figures) shown as blue lines. Response of remainder of group shown as group mean: for Case 1 (closed circles) n = 4; for Case 2 (who received only one dose) n = 15 receiving three doses (closed circles), and n = 4 receiving one dose (open circles). Error bars indicate SEM. Immunization days 0, 28, and/or 56 indicated by broad ticks crossing x-axis.
See this image and copyright information in PMC

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