Novel fusion antigen displayed-bacterial ghosts vaccine candidate against infection of Escherichia coli O157:H7

Abstract

Infection with Escherichia coli O157:H7 may develop into hemorrhagic colitis, or hemolytic uremic syndrome (HUS), which usually causes kidney failure or even death. The adhesion and toxins are the important virulent factors. In this study, a novel vaccine candidate rSOBGs was constructed based on the bacterial ghost (BG). rSOBGs maintained the integrity of cellular morphology and displayed the linear Stx2Am-Stx1B antigen on the surface of outer membrane. rSOBGs induced Stxs-specific IgA/IgG antibodies and stronger intimin-specific IgA/IgG antibodies effectively in sera in this study. In vivo, the rSOBGs provided the higher protection rate (52%) than native bacterial ghost-OBGs (12%) when challenged intragastricly with high dose (500 LD50) viable E. coli O157:H7. Meanwhile, the rSOBGs provided higher protection rate (73.33%) than OBGs when challenged with 2 LD50 even to 5 LD50 lysed E. coli O157:H7. In vitro, the rSOBGs-immunized sera possessed neutralizing activity to lysed pathogenic bacteria. Furthermore, the results of histopathology also displayed that the administration of rSOBGs have the ability to reduce or inhibit the adhesion lesions and toxins damages of organs. The novel vaccine candidate rSOBGs induced both anti-toxin and anti-adhesion immune protection, suggesting the possibility to prevent the infectious diseases caused by Escherichia coli O157:H7.

Protective Immunity Elicited by VP1 Chimeric Antigens of Bacterial Ghosts against Hand-Foot-and-Mouth Disease Virus

“…Samples were collected on days 0, 7, 14, 21, and 28 (3 mice were analyzed at each time point after the last immunization and were assayed for the presence of EVP1 and CVP1-specific antibodies by ELISA. Similar to our previous report [15], the specific antibodies induced by CBGs and EBGs increased persistently over time. We detected high levels of specific anti-EBGs and anti-CBGs IgG antibodies in the samples collected from mice immunized with BGs vaccine candidates.…”

“…A Vero E6 cell line and a HEp-2 cell line were kept in our lab. The expression vector pGEX was purchased from Transgen Inc. (Beijing, China), and display vector pSOMPA and lysis plasmid pLysisE were constructed by our lab [15]. Enterovirus 71 (EV71; GenBank: JQ514785.1) and coxsackievirus B3 (CB3; GenBank: M88483.1), on the basis of which vaccines have been developed, were kept in our lab.…”

“…BGs maintain the cellular morphology and native antigenic surface structure [10] and possess the adjuvant property of bacteria [11,12]. The effects of BG vaccines have been described in various pathogens, such as Vibriocholera [13], Helicobacterpylori [14], and Escherichia coli O157:H7 [15].…”

Immunization of mice with chimeric antigens displaying selected epitopes confers protection against intestinal colonization and renal damage caused by Shiga toxin-producing Escherichia coli

“…Despite these limitations, several STEC vaccine candidates have been evaluated in laboratory animals (mice, rats and rabbits) and in cattle, with promising results. They include Stx subunit-based vaccines [15][16][17] , protein and peptide-based vaccines [17][18][19][20][21] , attenuated bacteriabased vaccines 22 , bacterial ghost-based vaccines 23 , DNA-based vaccines 24,25 , and more recently nanoparticle-based vaccines 26 . While most of these vaccine candidates are based on LEE-encoded antigens and Stx subunits, there are several antigens encoded outside LEE that are expressed in vivo during human infection that could be suitable targets for vaccine development 13,27 .…”

Immunization of mice with chimeric antigens displaying selected epitopes confers protection against intestinal colonization and renal damage caused by Shiga toxin-producingEscherichia coli

“…12 Despite these limitations, several STEC vaccine candidates have been evaluated in laboratory animals (mice, rats and rabbits) and in cattle, with promising results. They include Stx subunit-based vaccines, 13–15 protein and peptide-based vaccines, 15–19 attenuated bacteria-based vaccines, 20 bacterial ghost-based vaccines, 21 DNA-based vaccines, 22, 23 and more recently nanoparticle-based vaccines. 24 While most of these vaccine candidates are based on LEE-encoded antigens and Stx subunits, there are several antigens encoded outside LEE that are expressed in vivo during human infection that could be suitable targets for vaccine development.…”