Abstract
BackgroundAn 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 The individual component(s) responsible for paralysis were not identified, and the vaccine was withdrawn.Methodology/Principal FindingsSubjects participating in two contemporaneous non-randomized Phase 1 clinical trials of nasal subunit vaccines against Human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/SignificanceWhile 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.
Highlights
Mucosal immunization via intranasal route has received much attention in recent years [1] due to potential advantages of needlefree delivery and enhanced mucosal immune responses against infections such as influenza or Human Immunodeficiency Virus (HIV), which can be enhanced by co-administration of effective mucosal adjuvants such as mutants of Escherichia coli heat labile toxin (LT) [2]
This immunization approach raised concerns after a strong epidemiological association was reported [3] between facial nerve paralysis (Bell’s Palsy) and intranasal administration of inactivated influenza virosome vaccine ‘‘NasalFlu’’ containing an enzymatically active mutant Labile Toxin (LT) adjuvant [4]
We report two cases of Bell’s palsy temporally associated with nasal administration of non-toxic LTK63, possibly a result of transient interference with peripheral nerve function due to accumulation of LTK63 molecules, or inflammation arising from immune response to LTK63, following ganglioside binding and retrograde neuronal transport; or another unknown mechanism
Summary
Mucosal immunization via intranasal route has received much attention in recent years [1] due to potential advantages of needlefree delivery and enhanced mucosal immune responses against infections such as influenza or Human Immunodeficiency Virus (HIV), which can be enhanced by co-administration of effective mucosal adjuvants such as mutants of Escherichia coli heat labile toxin (LT) [2] This immunization approach raised concerns after a strong epidemiological association was reported [3] between facial nerve paralysis (Bell’s Palsy) and intranasal administration of inactivated influenza virosome vaccine ‘‘NasalFlu’’ containing an enzymatically active mutant LT adjuvant [4]. The individual component(s) responsible for paralysis were not identified, and the vaccine was withdrawn
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