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Infect Immun, February 1998, p. 462-468, Vol. 66, No. 2
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Mucosal Immunogenicity of a Holotoxin-Like Molecule Containing the Serine-Rich Entamoeba histolytica Protein (SREHP) Fused to the A2 Domain of Cholera Toxin

Faisal Sultan,1,dagger Ling-ling Jin,1 Michael G. Jobling,2 Randall K. Holmes,2 and Samuel L. Stanley Jr.1,3,*

Departments of Medicine1 and Molecular Microbiology,3 Washington University School of Medicine, St. Louis, Missouri 63110, and Department of Microbiology, University of Colorado Health Sciences Center, Denver, Colorado 802622

Received 27 June 1997/Returned for modification 7 August 1997/Accepted 27 October 1997

One strategy for the induction of mucosal immune responses by oral immunization is to administer the antigen in conjunction with cholera toxin. Cholera toxin consists of one A polypeptide (CTA) which is noncovalently linked to five B subunits (CTB) via the A2 portion of the A subunit (CTA2). Coupling of antigens to the nontoxic B subunit of cholera toxin may improve the immunogenicity of antigens by targeting them to GM1 ganglioside on M cells and intestinal epithelial cells. Here, we describe the construction of a translational fusion protein containing the serine-rich Entamoeba histolytica protein (SREHP), a protective amebic antigen, fused to a maltose binding protein (MBP) and to CTA2. When coexpressed in Escherichia coli with the CTB gene, these proteins assembled into a holotoxin-like chimera containing MBP-SREHP-CTA2 and CTB. This holotoxin-like chimera (SREHP-H) inhibited the binding of cholera toxin to GM1 ganglioside. Oral vaccination of mice with SREHP-H induced mucosal immunoglobulin A (IgA) and serum IgG antiamebic antibodies and low levels of mucosal anti-CTB antibodies. Our studies confirm that the genetic coupling of antigens to CTA2 and their coexpression in E. coli can produce holotoxin-like molecules that are mucosally immunogenic without the requirement for supplemental cholera toxin, and they establish the SREHP-H protein as a candidate for evaluation as a vaccine to prevent amebiasis.

* Corresponding author. Mailing address: Washington University School of Medicine, Campus Box 8051, 660 S. Euclid Ave., St. Louis, MO 63110. Phone: (314) 362-1070. Fax: (314) 362-3525. E-mail: sstanley{at}im.wustl.edu.

dagger Present address: Shaukat Khanum Memorial Cancer Hospital and Research Center, Lahore, Pakistan.




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