Oral immunization of mice with a multivalent therapeutic subunit vaccine protects against Helicobacter pylori infection

Autor: Meiying Liu, Yu Liu, Ping Wang, Chongfa Tang, Yanbin Zhang, Xuewei Wang, Susan M. Logan, Bo Wei, Wangxue Chen, Jing Chen, Youxiu Zhong
Rok vydání: 2020
Předmět:
mice
Protein subunit
030231 tropical medicine
Administration
Oral
chemical and pharmacologic phenomena
medicine.disease_cause
Helicobacter Infections
03 medical and health sciences
Immunogenicity
Vaccine
0302 clinical medicine
Immune system
Adjuvants
Immunologic
Antigen
Immunity
medicine
Animals
Vaccines
Combined
030212 general & internal medicine
Th17 immune response
Antigens
Bacterial
Mice
Inbred BALB C
General Veterinary
General Immunology and Microbiology
biology
Toxin
business.industry
Immunogenicity
therapeutic vaccines
Public Health
Environmental and Occupational Health
mucosal adjuvant
Helicobacter pylori
biology.organism_classification
Antibodies
Bacterial
Urease
immune responses
Immunoglobulin A
Infectious Diseases
Immunization
Immunoglobulin G
Bacterial Vaccines
Vaccines
Subunit
Immunology
helicobacter pylori
bacteria
Molecular Medicine
business
Zdroj: Vaccine. 38:3031-3041
ISSN: 0264-410X
Popis: Helicobacter pylori is a human class I carcinogen and no effective prophylactic or therapeutic H. pylori vaccine has yet been marketed. H. pylori can escape the host immune response, but the precise immune protection mechanisms in humans remain unknown. In this study, we developed a multivalent, subunit H. pylori vaccine candidate by formulating three commonly used H. pylori antigens, neutrophil-activating protein (NAP), urease subunit A (UreA) and subunit B (UreB) with the mucosal adjuvant, a double-mutant heat-labile toxin (dmLT) from Escherichia coli, and evaluated its immunogenicity and therapeutic efficacy in a mouse model of H. pylori infection. We found that oral immunization of H. pylori-infected mice significantly reduced gastric bacterial colonization at both 2 and 8 weeks after immunization. The reduction in bacterial burdens was accompanied with significantly increased serum antigen-specific IgG responses and mucosal IgA responses. Moreover, oral immunization also induced Th1/Th17 immune responses, which may play a synergistic role with the specific antibodies in the elimination of H. pylori. Thus, our vaccine candidate appears able to overcome the immune evasion mechanism of H. pylori, restore the suppression of Th2 immune responses with the induction of a strong humoral immune response. These results lay the foundation for the development of an optimized oral therapeutic H. pylori vaccine with increased immunogenicity of UreA and UreB, as well as providing long-term immunity.
Databáze: OpenAIRE
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