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Infect. Immun. doi:10.1128/IAI.01740-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Safety and Immunogenicity of an ETEC Vaccine Patch Containing Heat-Labile Toxin: Use of Skin Pretreatment to Disrupt the Stratum Corneum

IOMAI Corporation, 20 Firstfield Road, Gaithersburg, Maryland 20878 USA; Center for Immunization Research, Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University, 624 North Broadway, Baltimore, Maryland, 21205 USA; Northwestern University School of Medicine, Department of Dermatology, 303 East Chicago Avenue, Chicago, Illinois 60611, USA

^* To whom correspondence should be addressed. Email: gglenn{at}iomai.com.

	Abstract

Transcutaneous immunization (TCI) allows safe delivery of native heat labile enterotoxin from E. coli (LT) via application of a simple patch. Physical disruption of the stratum corneum can improve the efficiency of delivery. In the current study, stratum corneum disruption was performed using an EKG prep pad prior to patch application. The effects were quantitated using transepidermal water loss (TEWL) and correlated with immune responses. 60 adults received 50µg of LT from 3 lots of LT (20 per group) administered in a patch at day 0 and day 21. The immunizations were well tolerated. No difference in anti-LT IgG were seen between the 3 LT lots, with a 100% seroconversion rate and a mean anti-LT IgG of 12,185 E.U. (24-fold rise). TEWL measurements performed at the second immunization were found to correlate with the day 42 individual fold rise in anti-LT IgG (r=0.59, p<0.001). In comparative assessment of immune responses, sera from an LT⁺/ST⁺ (E2447A) oral ETEC challenge, which induced moderate to severe diarrhea in 81% of recipients, contained anti-LT IgG titers of 3,245 E.U. (10.8-fold rise). Similarly, anti-LT IgG responses after an oral, CTB-containing cholera vaccine, which cross-reacts with LT and is protective against LT and LT/ST ETEC disease in the field, was 6,741 EU (3.3-fold rise). The study confirms that a well tolerated regimen for stratum corneum disruption before vaccine patch application results in robust immunity comparable to natural and vaccine induced immunity, and that the magnitude of stratum corneum disruption correlates with immune responses.