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.
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 [beta2-microglobulin (-/-)] but not MHC class II knockout mice [I-Ab (-/-)]. In B cell knockout mice [microMT (-/-)], 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.
Ermak
T H
TH
OraVax, Inc., Cambridge, Massachusetts 02139, USA.termak@oravax.com
Giannasca
P J
PJ
Nichols
R
R
Myers
G A
GA
Nedrud
J
J
Weltzin
R
R
Lee
C K
CK
Kleanthous
H
H
Monath
T P
TP
D000276:Adjuvants, Immunologic / Q000502:physiology; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D005753:Gastric Mucosa / Q000166:cytology / Q000276:immunology; D016481:Helicobacter Infections / Q000276:immunology / Q000517:prevention & control*; D016480:Helicobacter pylori / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D018928:Immunity, Mucosal; D007115:Immunization Schedule; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D013047:Specific Pathogen-Free Organisms; D013601:T-Lymphocytes / Q000276:immunology*; D014510:Urease / Q000276:immunology*; D014611:Vaccination
D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007136:Immunoglobulins; D014510:Urease