A comparison of murine and human immunoproteomes of Helicobacter pylori validates the preclinical murine infection model for antigen screening

Abstract

Preclinical mouse infection models are widely used for Helicobacter vaccine development, but how well such models mimic important aspects of human infections is unknown. A comparison of Helicobacter pylori immunoproteomes of infected mice with previously reported patient data reveals a high agreement in the antigens recognized, suggesting that H. pylori in vivo protein composition and recognition by the host immune system are comparable in mice and humans. Murine Helicobacter models may thus be valid to screen antigens for human vaccination.

FIG. 1.

Typical immunoproteome of H. pylori strain SS1 as revealed by two-dimensional gel electrophoresis and immunoblotting with sera from the same mouse obtained either prior to infection (A) or 14 weeks after infection (B). The immunoblots were stained with a peroxidase-coupled antibody to mouse immunoglobulins followed by chemiluminescence detection. To enhance the detection of weakly cross-reactive antigens, film A was exposed for a longer time period (15 min) than film B (5 min). Abbreviations: SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; IEF, isoelectric focusing.

FIG. 2.

Staining intensities of specifically recognized and cross-reactive (cross-r.) H. pylori antigens (top). The vertical lines represent the median values. For comparison, a histogram for the staining intensities of all detectable protein spots is shown at the bottom of the figure. Strongly immunogenic spots have higher staining intensities than those of all detectable spots (P < 0.001, t test), and cross-reactive species are significantly more intensely stained than specifically recognized species (P < 0.01, t test). a.u., arbitrary units.