Pig vaccination strategies based on enterotoxigenic Escherichia coli toxins

Abstract

Enterotoxigenic Escherichia coli (ETEC) are responsible for diarrhea in humans as well as in farm animals. ETEC infections in newborn, suckling, and especially in post-weaning piglets are associated with reduced growth rate, morbidity, and mortality. ETEC express virulence factors as adhesin and enterotoxins that play a central role in the pathogenic process. Adhesins associated with pigs are of diverse type being either fimbrial or non-fimbrial. Enterotoxins belong to two groups: heat-labile (LT) and heat-stable (ST). Heterogeneity of ETEC strains encompass expression of various fimbriae (F4, F5, F6, F18, and F41) and enterotoxins (LT, STa, STb, and EAST1). In the late years, attempts to immunize animals against neonatal and post-weaning diarrhea were focused on the development of anti-adhesin strategies as this is the initial step of ETEC pathogenesis. Although those vaccines demonstrated some protection against ETEC infections, as enterotoxins are pivotal to the virulence of ETEC, a new generation of vaccinal molecules, which include adhesin and one or more enterotoxins, were recently tested. Some of these newly developed chimeric fusion proteins are intended to control as well human diarrhea as enterotoxins are more or less common with the ones found in pigs. As these could not be tested in the natural host (human), either a mouse or pig model was substituted to evaluate the protection efficacy. For the advancement of pig vaccine, mice were sometimes used for preliminary testing. This review summarizes advances in the anti-enterotoxin immunization strategies considered in the last 10 years.

Evidence-Based Approaches for Determining Effective Target Antigens to Develop Vaccines against Post-Weaning Diarrhea Caused by Enterotoxigenic Escherichia coli in Pigs: A Systematic Review and Network Meta-Analysis

“…Hence, a bivalent vaccine combining both F4 fimbriae and LT enterotoxin would result in better protection than that provided by using only F18 fimbriae as it would produce both anti-adhesin and anti-enterotoxin antibodies. Similar findings have been reported in several other studies where immunization of piglets with a vaccine encoding for F4 fimbriae and enterotoxin antigens conferred complete protection against PWD and improved the daily weight gain in a virulent ETEC challenge model [ 60 , 61 ], whereas vaccination with F18 fimbriae alone did not prove as effective [ 76 , 79 ].…”

“…This difference in immunogenicity is due to the role of F4 and F18 fimbriae, and LT enterotoxin in inducing the immune response. The F4 fimbriae have a major structural subunit FaeG, which is highly immunogenic and is present in multiple copies on a single fimbriae [ 19 , 75 ], whereas the F18 ETEC presents a minor structural subunit FedF that serves as an adhesive subunit and is not effective in inducing anti-F18 antibody response [ 19 , 23 , 76 , 77 ]. The LT enterotoxin possesses great adjuvanticity that enhances vaccine-specific systemic and mucosal immune responses following mucosal or parenteral delivery [ 76 , 78 ].…”

“…The F4 fimbriae have a major structural subunit FaeG, which is highly immunogenic and is present in multiple copies on a single fimbriae [ 19 , 75 ], whereas the F18 ETEC presents a minor structural subunit FedF that serves as an adhesive subunit and is not effective in inducing anti-F18 antibody response [ 19 , 23 , 76 , 77 ]. The LT enterotoxin possesses great adjuvanticity that enhances vaccine-specific systemic and mucosal immune responses following mucosal or parenteral delivery [ 76 , 78 ]. Hence, a bivalent vaccine combining both F4 fimbriae and LT enterotoxin would result in better protection than that provided by using only F18 fimbriae as it would produce both anti-adhesin and anti-enterotoxin antibodies.…”

“…Regarding vaccine delivery, different studies have suggested that the oral route is the most logical route to deliver ETEC vaccines because vaccines administered through this route can rapidly induce the mucosal antibody response with secretory IgA secretion, which is critical for preventing bacterial colonization and neutralizing enterotoxins [ 19 , 76 ]. This immune response is hardly achieved by parenteral vaccines as they tend to induce systemic immunity rather than mucosal immunity [ 19 , 23 ].…”

Oral and Parenteral Vaccination against Escherichia coli in Piglets Results in Different Responses

“…Escherichia coli is a ubiquitous, universally distributed pathogen responsible for a large proportion of diarrhea in piglets, both neonatal and post-weaning diarrhea (PWD) [ 1 ]. The pathogenic action of E. coli depends on the adhesion elements present, as well as the ability to produce thermolabile toxins (LT), thermostable toxins (Sta and Stb) and verotoxins (VT1 and VT2) [ 1 , 2 ]. In fact, E. coli -related diseases may be considered one of the most economically costly diseases in the pig industry and, from a public health point of view, one of the most antibiotic-intensive in recent years.…”