Abstract | BACKGROUND: 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.
|
Authors | David J M Lewis, Zhiming Huo, Susan Barnett, Ingrid Kromann, Rafaela Giemza, Eva Galiza, Maria Woodrow, Birgit Thierry-Carstensen, Peter Andersen, Deborah Novicki, Giuseppe Del Giudice, Rino Rappuoli |
Journal | PloS one
(PLoS One)
Vol. 4
Issue 9
Pg. e6999
(Sep 16 2009)
ISSN: 1932-6203 [Electronic] United States |
PMID | 19756141
(Publication Type: Case Reports, Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
|
Chemical References |
- AIDS Vaccines
- Bacterial Toxins
- Enterotoxins
- Escherichia coli Proteins
- Gangliosides
- Tuberculosis Vaccines
- Vaccines, Inactivated
- heat-labile enterotoxin, E coli
|
Topics |
- AIDS Vaccines
(adverse effects)
- Adult
- Axons
(metabolism)
- Bacterial Toxins
(genetics)
- Bell Palsy
(etiology)
- Enterotoxins
(genetics)
- Escherichia coli
(metabolism)
- Escherichia coli Proteins
(genetics)
- Female
- Gangliosides
(chemistry)
- Humans
- Inflammation
- Male
- Mutation
- Protein Binding
- Tuberculosis Vaccines
(adverse effects)
- Vaccines, Inactivated
(adverse effects)
|