AUTHOR=Guo Le , Hong Dantong , Wang Shue , Zhang Fan , Tang Feng , Wu Tao , Chu Yuankui , Liu Hongpeng , He Meng , Yang Hua , Yin Runting , Liu Kunmei 

TITLE=Therapeutic Protection Against H. pylori Infection in Mongolian Gerbils by Oral Immunization With a Tetravalent Epitope-Based Vaccine With Polysaccharide Adjuvant

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.01185

DOI=10.3389/fimmu.2019.01185

ISSN=1664-3224

ABSTRACT=<p>Urease is an effective target for design of a therapeutic epitope vaccine against <italic>Helicobacter pylori</italic> (<italic>H. pylori</italic>). In our previous studies, an epitope vaccine CTB-UE containing Th and B epitopes from <italic>H. pylori</italic> urease was constructed, and the CTB-UE vaccine could provide therapeutic effect on <italic>H. pylori</italic> infection in mice. However, a multivalent vaccine, combining different antigens participating in different aspects of <italic>H. pylori</italic> colonization and pathogenesis, may be more effective as a therapeutic vaccine than a univalent vaccine targetting urease. Therefore, a multivalent epitope vaccine FVpE, containing Th1-type immune adjuvant NAP, three selected functional fragments from CagA and VacA, and an urease multi-epitope peptide (UE) from CTB-UE, was constructed in this study and expected to obtain better sterilizing immunity than the univalent epitope vaccine CTB-UE. The therapeutic effect of multivalent epitope vaccine FVpE with polysaccharide adjuvant (PA) was evaluated in <italic>H. pylori</italic>-infected Mongolian gerbil model. The results showed that both FvpE and CTB-UE vaccine could induce similar levels of specific antibodies against <italic>H. pylori</italic> urease, and had similar inhibition effect on <italic>H. pylori</italic> urease activity. However, only FVpE could induce high levels of specific antibodies to CagA, VacA, and NAP. In addition, oral therapeutic immunization with FVpE plus PA significantly reduced the number of <italic>H. pylori</italic> colonies in the stomach of Mongolian gerbils compared with oral immunization with CTB-UE plus PA, or FVpE only, and the FVpE vaccine with PA even exhibited sterilizing immunity. The protection of FVpE was related to the mixed CD4<sup>+</sup> T cell responses and epitope-specific antibodies against various <italic>H. pylori</italic> antigens. These results indicate that a multivalent epitope vaccine targetting various <italic>H. pylori</italic> antigens could be a promising candidate against <italic>H. pylori</italic> infection.</p>