CN-108495650-B - Helicobacter pylori vaccine

Abstract

The present invention relates to immunogenic compositions and their use in the prevention or treatment of diseases or conditions caused by or associated with helicobacter pylori (Helicobacter pylori), particularly helicobacter pylori (h.pyri) infection and gastroduodenal conditions caused by helicobacter pylori. The invention also relates to a method for detecting helicobacter pylori infection in a subject.

Inventors

• Tobias Cruze
• Daniel Hornberg
• Marcus Gerhard
• Matias Mann
• Felix Meisner

Assignees

• 慕尼黑工业大学
• 慕尼黑工业大学
• 马普协会
• 马普协会

Dates

Publication Date

20260421

Application Date

20161214

Priority Date

20151214

Claims (13)

1. 1. An immunogenic composition comprising: (a) At least one isolated polypeptide or peptide consisting of (i) the amino acid sequence of SEQ ID NO.1, or (ii) a variant of SEQ ID NO. 15 lacking an N-terminal signal sequence of (i); (b) A fusion protein comprising an isolated polypeptide or peptide according to item (a), or (C) At least one nucleic acid molecule encoding an isolated polypeptide or peptide according to item (a) or a fusion protein according to item (b).
2. 2. The immunogenic composition of claim 1, wherein the isolated polypeptide or peptide is a recombinant polypeptide or peptide.
3. 3. The immunogenic composition of claim 1, further comprising at least one additional antigen from helicobacter pylori (h.pyri).
4. 4. The immunogenic composition of claim 1, wherein the immunogenic composition comprises the fusion protein.
5. 5. The immunogenic composition of claim 1, wherein the nucleic acid molecule is DNA or RNA.
6. 6. The immunogenic composition of claim 5, wherein the nucleic acid molecule is contained in a vector.
7. 7. The immunogenic composition of claim 1, further comprising at least one adjuvant.
8. 8. The immunogenic composition of claim 1, which is a vaccine.
9. 9. Use of an immunogenic composition according to any one of claims 1 to 8 in the manufacture of a medicament for the prevention of a disease or condition caused by helicobacter pylori.
10. 10. The use according to claim 9, wherein the disease or condition is helicobacter pylori infection.
11. 11. The use according to claim 9, wherein the disease or condition is a gastroduodenal condition caused by helicobacter pylori.
12. 12. The use according to claim 11, wherein the gastroduodenal disorder is selected from the group consisting of gastritis, gastric or duodenal ulcers, gastric cancer and MALT lymphoma.
13. 13. The use according to claim 12, wherein the gastritis is chronic gastritis.

Description

Helicobacter pylori vaccine Technical Field The present invention relates to immunogenic compositions and their use in the prevention or treatment of diseases or conditions caused by or associated with helicobacter pylori (Helicobacter pylori), particularly helicobacter pylori (h.pyri) infection and gastroduodenal conditions caused by helicobacter pylori. The invention also relates to a method for detecting helicobacter pylori infection in a subject. Background Helicobacter pylori (h.pyri) is a microaerophilic gram-negative bacterium that persists throughout the human stomach. Helicobacter pylori infection is the most common bacterial infectious disease in humans, and according to the socioeconomic status of the region, one half of the world population is infected with helicobacter pylori (Perez-Perez et al, 2004). Such infections are associated with many gastric diseases, such as chronic atrophic gastritis, peptic ulcers, gastric or stomach cancers and mucosa-associated lymphoid tissue (mucosa associated lymphoid tissue, MALT) lymphomas (Nomura et al, 1994; forman,1996; parsonnet et al, 1991; blaser et al, 1995). Helicobacter pylori is the leading cause of gastric cancer (the third most common type of cancer, with 983.000 cases worldwide in 2011) (Jemal et al, 2011). Gastric cancer is accompanied by considerable socioeconomic costs. The cost of treating a gastric cancer patient is currently about 50,000 euros. Prevention of gastric cancer involves early treatment of infections caused by helicobacter pylori. It is estimated that at least one third of individuals suffering from infections caused by helicobacter pylori require treatment. Currently, it is difficult to predict which patients will develop subsequent diseases associated with helicobacter pylori infection. According to the results of a large number of studies, general treatment of helicobacter pylori infection to prevent gastric cancer is cost-effective, as it will prevent more than 95% of cases (Graham & Shiotani, 2005). Patients with gastric ulcers, precancerous or definitive gastric cancer, relatives of gastric cancer patients, and patients in need of long-term non-steroidal anti-inflammatory drug treatment (including aspirin for cardiovascular disease) are specifically indicated for treatment. Since the rate of gastric cancer is high in japan, it is suggested therein that all individuals infected with helicobacter pylori are treated, but the antibiotic resistance rate is steadily increased (Shiota et al, 2010). To date, the standard treatment of infections caused by helicobacter pylori consists of two antibiotics in combination with a proton pump inhibitor (e.g. omeprazole). The cost of one week of treatment is about 200 euros per patient. This treatment has significant side effects in some patients and results in a dramatic increase in resistant pathogens. Since two-wire and three-wire therapies often fail, more than 10% of all patients are no longer receiving therapy (Gao et al, 2010), estimated that they may rise to 60% by 2020. Millions of patients can benefit and medical costs can be significantly reduced if a vaccine against helicobacter pylori is available. Vaccines are highly effective against epidemic infectious diseases. In fact, the U.S. center of Disease Control for disease control is called vaccination as the most effective method for preventing infectious diseases (U.S. cdc, 2011). However, to date, no effective vaccine for humans against helicobacter pylori has been available. Phase II clinical trials of Novartis in 2010 with three antigen (CagA, vacA, napA) -based helicobacter pylori vaccines were considered unsuccessful. Since these antigens are very variable and are present only in some helicobacter pylori strains, only partial protection is expected. It is therefore an object of the present invention to identify helicobacter pylori polypeptides which elicit an immune response in a subject and which are suitable as flood protective vaccines against helicobacter pylori. It is a further object of the present invention to provide immunogenic compositions comprising one or more of these polypeptides/antigens, which compositions are useful for the prevention or treatment of diseases or conditions caused by or associated with helicobacter pylori. It is another object of the present invention to identify polypeptides/antigens that can be used as biomarkers for helicobacter pylori infection and to provide methods for detecting helicobacter pylori infection in a subject based on the use thereof. Summary of The Invention In one aspect, the invention relates to an immunogenic composition comprising: (a) At least one isolated (poly) peptide comprising (i) an amino acid sequence selected from the group consisting of SEQ ID NOs 1 to 7, or (ii) an immunogenic variant of (i), or (iii) an immunogenic fragment of (i) or (ii), or (B) At least one nucleic acid molecule encoding the isolated (poly) peptide according to item (a). In one embodiment