Oral immunization with attenuated Salmonella vaccine expressing Escherichia coli O157:H7 intimin gamma triggers both systemic and mucosal humoral immunity in mice

Abstract

Human infections with EHEC such as O157:H7 have been a great concern for worldwide food-industry surveillance. This pathogen is commonly associated with bloody diarrhea that can evolve to the lifethreatening hemolytic uremic syndrome. Animals are the natural reservoir where this pathogen remains asymptomatically, in steps of ingestion and colonization of the bowel. The bacterium is shed in the feces, contaminating the surroundings, including water and food that are directed for human consumption. A major player in this colonization process is intimin, an outer membrane adhesion molecule encoded by the E. coli attachment and effacement (eae) gene that has been shown to be essential for intimate bacterial attachment to eukaryotic host cells. In an attempt to reduce the colonization of animal reservoirs with EHEC O157:H7, we designed a vaccine model to induce an immune response against intimin gamma. The model is based on its recombinant expression in attenuated Salmonella, used as a suitable vaccine vector because of its recognized ability to deliver recombinant antigens and to elicit all forms of immunity: mucosal, systemic, and humoral responses. To test this model, mice were orally immunized with a S. enterica serovar Typhimurium strain carrying the pYA3137eaeA vector, and challenged with E. coli O157:H7. Here we show that immunization induced the production of high levels of specific IgG and IgA antibodies and promoted reduction in the fecal shedding of EHEC after challenge. The live recombinant vaccine reported herein may contribute to the efforts of reducing animal intestinal mucosa colonization.

Common Features of Mucosal and Peripheral Antibody Responses Elicited by Candidate HIV-1 Vaccines in Rhesus Monkeys

“…The RV144 clinical trial suggested that vaccine-elicited HIV-1 envelope (Env)-specific humoral immune responses may have contributed to the partial protection observed for vaccinees (2), but mucosal immune responses were not assessed in that trial. In contrast, previous studies have shown that immunization with peptide, DNA, protein, or attenuated bacterial or viral vector-based vaccines through parental or mucosal routes may elicit antigen-specific humoral immune responses at mucosal sites in mice, nonhuman primates, and humans (3)(4)(5)(6)(7). However, the characteristics, functionality, and epitope specificity of vaccine-elicited mucosal antibody responses have not been fully explored.…”

Intestinal Pathogenic Escherichia coli: Insights for Vaccine Development

“…The attenuated bacteria expressing intimin were still detectable in Peyer's patches and spleen, while in feces CFUs decreased in number from day 2 to 10 and subsequently were constant. Animals immunized with the attenuated Salmonella had reduced EHEC O157:H7 shedding post-challenge and increased production of IgA and IgG (Oliveira et al, 2012 ).…”

Advances in the development of enterohemorrhagic Escherichia coli vaccines using murine models of infection

“…Orally inoculated Salmonella enterica serovar Typhimurium x3987 expresing intimin was able to colonize the mice Peyer's patches and spleen, producing specific serum IgG and fecal IgA antibodies and reducing EHEC shedding after challenge [78]. Lactobacillus lactis expressing EspA or EspB induced antigen-specific humoral IgG responses.…”