Methods for preventing the development of a gastric disease associated with helicobacter pylori infection without eradicating the infection and for the assessment of the risk of developing such disease

A method for preventing, alleviating and/or treating a gastric disease in a subject diagnosed with H. pylori infection, comprising administering to the subject an effective amount of a vaccine composition containing an antigen wherein the administration of said antigen results in the induction of an antibody response that targets a conserved structural epitope in the Carbohydrate Binding Domain (CBD) of the ABO/Leb-Blood group Antigen-Binding Adhesin (BabA), sufficient to reduce mucosal attachment of H. pylori without eradicating the H. pylori infection in said subject,

• wherein said gastric disease is chosen from gastroesophageal reflux disease (GERD), chronic active gastritis (GA), peptic ulcer disease (DU), gastric ulcer disease, and gastric cancer;
• wherein the antigen is a recombinant modified BabA exhibiting conserved structural epitopes including four disulfide bonds whereof the second disulfide bond spans seven amino acids between two adjacent cystein molecules, having an amino acid sequence with at least 80% identity, such as at least 85% identity, such as at least 90% identity, or at least 95% identity with the sequence defined by SEQ ID NO. 2;
• and
• wherein the composition is formulated as a vaccine comprising a pharmaceutically acceptable carrier and an adjuvant chosen from mucosal or systemic adjuvants that preferentially activate the humoral immune responses with induction of protective antibodies.

A method for preventing, alleviating and/or treating a gastric disease in a subject diagnosed with H. pylori infection, comprising administering to the subject an effective amount of a vaccine composition containing an antigen wherein the administration of said antigen results in the induction of an antibody response that targets a conserved structural epitope in the Carbohydrate Binding Domain (CBD) of the ABO/Leb-Blood group Antigen-Binding Adhesin (BabA), sufficient to reduce mucosal attachment of H. pylori without eradicating the H. pylori infection in said subject;

• wherein said gastric disease is chosen from gastroesophageal reflux disease (GERD), chronic active gastritis (GA), peptic ulcer disease (DU), gastric ulcer disease, and gastric cancer;
• wherein the antigen is a recombinant modified BabA exhibiting conserved structural epitopes including four disulfide bonds whereof the second disulfide bond spans seven amino acids between two adjacent cystein molecules, having an amino acid sequence with at least 80% identity, such as at least 85% identity, such as at least 90% identity, or at least 95% identity with the sequence defined by SEQ ID NO. 2;
• wherein the composition is formulated as a vaccine comprising a pharmaceutically acceptable carrier and an adjuvant chosen from mucosal or systemic adjuvants that preferentially activate the humoral immune responses with induction of protective antibodies;
• and
• wherein the antigen is structurally stabilized by the incorporation of a continuous sequence of at least four positive amino acids is included in said sequence, preferably at the C-terminal of said sequence.

A vaccine formulation comprising an immunogenically effective amount of an antigen for use in a method of preventing or treating gastric disease in a subject diagnosed with Helicobacter pylori (H. pylori) infection,

• wherein said antigen is capable of inducing an antibody response sufficient to reduce mucosal attachment of H. pylori without eradicating the H. pylori infection;
• wherein said antibody response specifically targets a conserved structural epitope in the Carbohydrate Binding Domain (CBD) of the ABO/Leb-Blood group Antigen-Binding Adhesin (BabA) of H. pylori;
• wherein said antigen is a recombinant modified BabA exhibiting conserved structural epitopes including four disulfide bonds whereof the second disulfide bond spans seven amino acids between two adjacent cystein molecules, having an amino acid sequence with at least 80% identity, such as at least 85% identity, such as at least 90% identity, or at least 95% identity with the sequence defined by SEQ ID NO. 2;
• wherein said gastric disease is chosen from gastroesophageal reflux disease (GERD), chronic active gastritis (GA), peptic ulcer disease (DU), gastric ulcer disease, and gastric cancer, and
• wherein the composition comprises a pharmaceutically acceptable carrier and an adjuvant chosen from mucosal or systemic adjuvants that preferentially activate the humoral immune responses with induction of protective antibodies.