Oral Immunization With a M Cell-Targeting Recombinant L. Lactis Vaccine LL-plSAM-FVpE Stimulate Protective Immunity Against H. Pylori in Mice

Abstract

There are many virulence factors of <i>H. pylori</i> that contribute in diverse ways to gastric disease. Therefore, designing multivalent epitope vaccines against many key virulence factors virulence factors of <i>H. pylori</i> is a promising strategy to control <i>H. pylori</i> infection. In previous studies, we constructed a multivalent epitope vaccine FVpE against four key virulence factors of <i>H. pylori</i> (Urease, CagA, VacA, and NAP), and oral immunization with the FVpE vaccine plus a polysaccharide adjuvant (PA) containing <i>lycium barbarum</i> polysaccharide and chitosan could provide protection against <i>H. pylori</i> infection in the Mongolian gerbil model. Oral vaccines have many advantages over injected vaccines, such as improved safety and compliance, and easier manufacturing and administration. However, the harsh gastrointestinal (GI) environment, such as gastric acid and proteolytic enzymes, limits the development of oral vaccines to some extent. Oral vaccines need a gastrointestinal delivery system with high safety, low price and promoting vaccine antigen to stimulate immune response in the gastrointestinal mucosa. Lactic acid bacteria are gastrointestinal probiotics that have unique advantages as a delivery system for oral vaccines. In this study, a M cell-targeting surface display system for <i>L. lactis</i> named plSAM was designed to help vaccine antigens to stimulate effective immune responses in the gastrointestinal tract, and a M cell-targeting recombinant <i>L. lactis</i> vaccine LL-plSAM-FVpE was constructed by using the surface display system plSAM. recombinant <i>L. lactis</i> vaccine LL-plSAM-FVpE could secretively express the SAM-FVpE protein and display it on the bacterial surface. Moreover, experimental results confirmed that LL-plSAM-FVpE had an enhanced M cell-targeting property. In addition, LL-plSAM-FVpE had excellent M cell-targeting property to promote the phagocytosis and transport of the antigen SAM-FVpE by gastrointestinal M cells. More importantly, oral immunization of LL-plSAM-FVpE or SAM-FVpE plus PA can stimulate IgG and sIgA antibodies and CD4⁺ T cell immune responses against four virulence factors of <i>H. pylori</i> (Urease, CagA, VacA, and NAP), thus providing protective immunity against <i>H. pylori</i> infection in mice. The M cell-targeting recombinant <i>L. lactis</i> vaccine against various key <i>H. pylori</i> virulence factors could be a promising vaccine candidate for controlling <i>H. pylori</i> infection.