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Infection and Immunity, March 2002, p. 1056-1068, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1056-1068.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Transcutaneous Immunization Using Colonization Factor and Heat-Labile Enterotoxin Induces Correlates of Protective Immunity for Enterotoxigenic Escherichia coli

Jianmei Yu,1,2 Frederick Cassels,3 Tanya Scharton-Kersten,2 Scott A. Hammond,1,2 Antoinette Hartman,3 Evelina Angov,4 Blaise Corthésy,5 Carl Alving,1 and Gregory Glenn1,2*

Department of Membrane Biochemistry,1 Department of Enteric Infections,3 Department of Immunology,4 Walter Reed Army Institute of Research, Silver Spring, and IOMAI Corporation, Gaithersburg, Maryland,2 Division of Immunology and Allergy, R & D Laboratory, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland5

Received 17 July 2001/ Returned for modification 15 October 2001/ Accepted 6 November 2001

Enterotoxigenic Escherichia coli (ETEC) diarrheal disease is a worldwide problem that may be addressed by transcutaneous delivery of a vaccine. In several human settings, protective immunity has been associated with immune responses to E. coli colonization factors and to the heat-labile toxin that induces the diarrhea. In this set of animal studies, transcutaneous immunization (TCI) using recombinant colonization factor CS6 and cholera toxin (CT) or heat-labile enterotoxin (LT) as the adjuvant induced immunoglobulin G (IgG) and IgA anti-CS6 responses in sera and stools and antibody responses that recognized CS6 antigen in its native configuration. The antitoxin immunity induced by TCI was also shown to protect against enteric toxin challenge. Although immunization with LT via the skin induced mucosal secretory IgA responses to LT, protection could also be achieved by intravenous injection of the immune sera. Finally, a malaria vaccine antigen, merzoite surface protein 142 administered with CT as the adjuvant, induced both merzoite surface protein antibodies and T-cell responses while conferring protective antitoxin immunity, suggesting that both antiparasitic activity and antidiarrheal activity can be obtained with a single vaccine formulation. Overall, our results demonstrate that relevant colonization factor and antitoxin immunity can be induced by TCI and suggest that an ETEC traveler's diarrhea vaccine could be delivered by using a patch.

* Corresponding author. Mailing address: IOMAI Corporation, 20 Firstfield Road, Suite 250, Gaithersburg, MD 20878. Phone: (301) 556-4500. Fax: (301) 556-4501. E-mail: gglenn{at}iomai.com.

Infection and Immunity, March 2002, p. 1056-1068, Vol. 70, No. 3
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.3.1056-1068.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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