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Infection and Immunity, September 2000, p. 5306-5313, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Transcutaneous Immunization with Bacterial ADP-Ribosylating Exotoxins, Subunits, and Unrelated Adjuvants

Tanya Scharton-Kersten,1,2 Jian-mei Yu,1,2 Russell Vassell,1,2 Derek O'Hagan,3 Carl R. Alving,1 and Gregory M. Glenn1,2,*

Department of Membrane Biochemistry, Walter Reed Army Institute of Research,1 and IOMAI Corporation,2 Washington, D.C., and Chiron Corporation, Emeryville, California3

Received 29 December 1999/Returned for modification 28 February 2000/Accepted 13 June 2000

We have recently described a needle-free method of vaccination, transcutaneous immunization, consisting of the topical application of vaccine antigens to intact skin. While most proteins themselves are poor immunogens on the skin, we have shown that the addition of cholera toxin (CT), a mucosal adjuvant, results in cellular and humoral immune responses to the adjuvant and coadministered antigens. The present study explores the breadth of adjuvants that have activity on the skin, using diphtheria toxoid (DTx) and tetanus toxoid as model antigens. Heat-labile enterotoxin (LT) displayed adjuvant properties similar to those of CT when used on the skin and induced protective immune responses against tetanus toxin challenge when applied topically at doses as low as 1 µg. Interestingly, enterotoxin derivatives LTR192G, LTK63, and LTR72 and the recombinant CT B subunit also exhibited adjuvant properties on the skin. Consistent with the latter finding, non-ADP-ribosylating exotoxins, including an oligonucleotide DNA sequence, as well as several cytokines (interleukin-1beta [IL-1beta ] fragment, IL-2, IL-12, and tumor necrosis factor alpha) and lipopolysaccharide also elicited detectable anti-DTx immunoglobulin G titers in the immunized mice. These results indicate that enhancement of the immune response to topical immunization is not restricted to CT or the ADP-ribosylating exotoxins as adjuvants. This study also reinforces earlier findings that addition of an adjuvant is important for the induction of robust immune responses to vaccine antigens delivered by topical application.

* Corresponding author. Mailing address: Walter Reed Army Institute of Research, Attn: IOMAI Corp., Rm. 2W124, 503 Robert Grant Rd., Silver Spring, MD 20910-7500. Phone: (301) 319-9391. Fax: (301) 319-9395. E-mail: gglenn{at}iomai.com.

Infection and Immunity, September 2000, p. 5306-5313, Vol. 68, No. 9
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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