The Journal of Experimental Medicine
VeriKine-HS Human IFN-Beta
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© The Rockefeller University Press, 0022-1007/1998/12/2277/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 12, December 21, 1998 2277-2288

Articles

Immunization of Mice with Urease Vaccine Affords Protection against Helicobacter pylori Infection in the Absence of Antibodies and Is Mediated by MHC Class II–restricted Responses

Thomas H. Ermak*, Paul J. Giannasca*, Richard Nichols*, Gwendolyn A. Myers*, John Nedrud{ddagger}, Richard Weltzin*, Cynthia K. Lee*, Harold Kleanthous*, and Thomas P. Monath*

From * OraVax, Inc., Cambridge, Massachusetts 02139; and {ddagger} Case Western Reserve University, Cleveland, Ohio 44106

We examined the roles of cell- and antibody-mediated immunity in urease vaccine–induced protection against Helicobacter pylori infection. Normal and knockout mice deficient in major histocompatibility complex (MHC) class I, MHC class II, or B cell responses were mucosally immunized with urease plus Escherichia coli heat-labile enterotoxin (LT), or parenterally immunized with urease plus aluminum hydroxide or a glycolipid adjuvant, challenged with H. pylori strain X47-2AL, and H. pylori organisms and leukocyte infiltration in the gastric mucosa quantified. In an adjuvant/route study in normal mice, there was a direct correlation between the level of protection and the density of T cells recruited to the gastric mucosa. In knockout studies, oral immunization with urease plus LT protected MHC class I knockout mice [β2-microglobulin (–/–)] but not MHC class II knockout mice [I-Ab (–/–)]. In B cell knockout mice [µMT (–/–)], vaccine-induced protection was equivalent to that observed in immunized wild-type (+/+) mice; no IgA+ cells were detected in the stomach, but levels of CD4+ cells equivalent to those in the wild-type strain (+/+) were seen. These studies indicate that protection of mice against H. pylori infection by immunization with the urease antigen is dependent on MHC class II–restricted, cell-mediated mechanisms, and antibody responses to urease are not required for protection.

Key Words: Helicobacter pylori • knockout mice • adjuvants • gastric mucosa • T cells

Address correspondence to Thomas Ermak, OraVax, Inc., 38 Sidney St., Cambridge, MA 02139. Phone: 617-494-1339; Fax: 617-494-0927; E-mail: termak{at}oravax.com

Abbreviations used: β2m, β2-microglobulin; H & E, hematoxylin and eosin; IEL, intraepithelial lymphocytes; IN, intranasal; LT, Escherichia coli heat-labile toxin; urease-ACC, urease-specific antibody–containing cells.


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