Transcutaneous immunization, a topical vaccine application, combines the advantages of needle-free delivery while targeting the immunologically rich milieu of the skin. In animal studies, this simple technique induces robust systemic and mucosal antibodies against vaccine antigens. Here, we demonstrate safe application of a patch containing heat-labile enterotoxin (LT, derived from Escherichia coli) to humans, resulting in robust LT-antibody responses. These findings indicate that TCI is feasible for human immunization, and suggest that TCI may enhance efficacy as well as improve vaccine delivery.
We studied the safety and immunogenicity of a Shigella flexneri 2a vaccine comprising native S. flexneri 2a lipopolysaccharide (LPS) complexed to meningococcal outer membrane proteins-proteosomes-in normal, healthy adults. A two-dose series of immunizations was given by intranasal spray, and doses of 0.1, 0.4, 1.0, and 1.5 mg (based on protein) were studied in a dose-escalating design. The vaccine was generally well tolerated. The most common reactions included rhinorrhea and nasal stuffiness, which were clearly dose related (P < 0.05). These reactions were self-limited and generally mild. The vaccine elicited S. flexneri 2a LPS-specific immunoglobulin A (IgA), IgG, and IgM antibody-secreting cells (ASCs) in a dose-responsive manner. At doses of 1.0 or 1.5 mg, highly significant (P < 0.001) increases in ASCs of all antibody isotypes occurred and 95% of subjects had an ASC response in at least one antibody isotype. Dose-related serum antibody responses were observed, with geometric mean two-to fivefold rises in specific serum IgA and IgG titers and two-to threefold rises in IgM in the 1.0-and 1.5-mg-dose groups (P < 0.0001 for each isotype). Elevated serum antibody levels persisted through day 70. Increases in fecal IgG and IgA and also in urinary IgA specific for S. flexneri 2a LPS were demonstrated. These were most consistent and approached statistical significance (P ؍ 0.02 to 0.12 for various measures) on day 70 after the first dose. The magnitude of immune responses to intranasally administered proteosome-S. flexneri 2a LPS vaccine is similar to those reported for live vaccine candidates associated with protective efficacy in human challenge models, and further evaluation of this product is warranted.
BACKGROUND
Keratoacanthomas (KAs) are common tumors of squamous cell origin that grow rapidly and may regress; however, differentiation from an aggressive squamous cell carcinoma is problematic.
OBJECTIVE
To report the authors' experience in managing KA with intralesional methotrexate (MTX) or surgical excision.
MATERIALS AND METHODS
The authors collected data on 157 tumors (136 patients) over 6 months from a single institution.
RESULTS
There were 73 tumors (54 patients) treated with intralesional MTX. There were 9 tumors that did not resolve with intralesional MTX (88% cure). Nonresolving tumors were excised with no recurrences or complications. In all 9 cases, the nonresolving tumors were of the same size or smaller after MTX. Of the 73 tumors treated with MTX, 29 tumors (11 patients) were multiple KAs. All 29 tumors resolved (100% tumor clearance). There were no complications in any of the MTX-treated patients. Tumor clearance was defined by clinical resolution for a minimum of 6 weeks without a recurrence. There were 84 tumors (83 patients) treated with surgical excision. There were no complications and no recurrences (100% cure) with surgery.
CONCLUSION
Intralesional MTX may be considered as the initial treatment for solitary KA, multiple KA, or in poor surgical candidates.
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