Immunogenicity and protective efficacy of a single-dose live non-pathogenic Escherichia coli oral vaccine against F4-positive enterotoxigenic Escherichia coli challenge in pigs

Fairbrother, John M.; Nadeau, Éric; Bélanger, Louise; Tremblay, Cindy-Love; Tremblay, D.; Brunelle, Mélanie; Wolf, Regina; Hellmann, Klaus; Hidalgo, Álvaro

doi:10.1016/j.vaccine.2016.11.045

Cited by 46 publications

(61 citation statements)

References 28 publications

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“…This can stimulate the intestinal colonization by these E. coli which induces the secretion of intestinal antibodies, and finally blocks the adherence of ETEC. A wide range of on-farm studies have shown a reduced mortality and reduced use of antibiotics after oral administration of a live attenuated or live non-enterotoxigenic F4 + E. coli strain to pigs immediately after weaning ( Fuentes et al., 2004 , Ruan and Zhang, 2013 , Fairbrother et al., 2016 ).…”

Section: Applications Of Preventing Postweaning Diarrhea Associated Wmentioning

confidence: 99%

Intestinal challenge with enterotoxigenic Escherichia coli in pigs, and nutritional intervention to prevent postweaning diarrhea

Sun

Kim

2017

Animal Nutrition

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Gut health of nursery pigs immediately after weaning is tightly associated with their growth performance and economic values. Postweaning diarrhea (PWD) is one of the major concerns related to gut health of nursery pigs which often is caused by infections of enterotoxigenic Escherichia coli (ETEC), mainly including F4 (K88)+ and F18+E. coli. The main virulence factors of ETEC are adhesins (fimbriae or pili) and enterotoxins. The common types of fimbriae on ETEC from PWD pigs are F18+ and F4+. Typically, PWD in pigs is associated with both F18+ and F4+ ETEC infections whereas pre-weaning diarrhea in pigs is associated with F4+ ETEC infection. Enterotoxins including heat-labile enterotoxins (LT) and heat-stable peptide toxins (ST) are associated with causing diarrhea in pigs. At least 109 to 1010 ETEC are required to induce diarrhea in nursery pigs typically lasting 1 to 5 days after ETEC infection. Antibiotics used to be the most effective way to prevent PWD, however, with the increased bacterial resistance to antibiotics, alternatives to the use of antibiotics are urgently needed to prevent PWD. Immunopropylaxis and nutritional intervention of antimicrobial minerals (such as zinc oxide and copper sulfate), organic acids, functional feedstuffs (such as blood plasma and egg yolk antibodies), direct fed microbials, phytobiotics, and bacteriophage can potentially prevent PWD associated with ETEC. Some other feed additives such as nucleotides, feed enzymes, prebiotic oligosaccharides, and clay minerals can enhance intestinal health and thus indirectly help with preventing PWD. Numerous papers show that nutritional intervention using selected feed additives can effectively prevent PWD.

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Section: Applications Of Preventing Postweaning Diarrhea Associated Wmentioning

confidence: 99%

Intestinal challenge with enterotoxigenic Escherichia coli in pigs, and nutritional intervention to prevent postweaning diarrhea

Sun

Kim

2017

Animal Nutrition

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“…[ 61 , 62 ]. Coliprotec ® F4 (Prevtec Microbia GmbH, Montrela, Canada) [ 63 ] and the recently reported oral bivalent F4/F18 vaccine [ 64 ] are attenuated vaccines designed for the active immunization of pigs against PWD, but there are no data available on their effect in sows.…”

Section: Different Types Of Vaccinesmentioning

confidence: 99%

Maternal Vaccination. Immunization of Sows during Pregnancy against ETEC Infections

et al. 2017

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The immunology of pregnancy is an evolving consequence of multiple reciprocal interactions between the maternal and the fetal-placental systems. The immune response must warrant the pregnancy outcome (including tolerance to paternal antigens), but at the same time, efficiently respond to pathogenic challenges. Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and death in neonatal and recently weaned pigs. This review aims to give an overview of the current rationale on the maternal vaccination strategies for the protection of the newborn pig against ETEC. Newborn piglets are immunodeficient and naturally dependent on the maternal immunity transferred by colostrum for protection—a maternal immunity that can be obtained by vaccinating the sow during pregnancy. Our current knowledge of the interactions between the pathogen strategies, virulence factors, and the host immune system is aiding the better design of vaccination strategies in this particular and challenging host status. Challenges include the need for better induction of immunity at the mucosal level with the appropriate use of adjuvants, able to induce the most appropriate and long-lasting protective immune response. These include nanoparticle-based adjuvants for oral immunization. Experiences can be extrapolated to other species, including humans.

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“…2A, B). (Table 3) and IPEC-J2 (Table 4) (20,21,41,43). Furthermore, in contrast to other fimbriae, the adhesive subunit of F18 fimbriae is its minor subunit, thus purified F18 fimbriae is unable to induce anti-F18 antibodies and provide protection from PWD caused by F18+ ETEC strains (22).…”

Section: Mouse Serum Antibody Adherence Inhibition Assaymentioning

confidence: 99%

“…Vaccination with either purified fimbriae or adhesive subunits of fimbriae are reported to be efficacious in protecting and controlling piglet PWD (15)(16)(17)(18)(19). Currently, Fairbrother et al demonstrated that weaned piglets oral vaccinated with a single-dose live monovalent F4 vaccine (Coliprote ○ R F4, Prevtec Microbia) can protect immunized piglets against a F4+ ETEC challenge at 3, 7 or 21 days (20). Further, Nadeau et al demonstrated that weaned piglets administrated with a single oral dose of a bivalent F4/F18 vaccine (Coliprote ○ R F4/F18, Prevtec Microbia) can protect immunized piglets challenged with both F4+ and F18+ ETEC (21).…”

Section: Introductionmentioning

confidence: 99%

Coimmunization with Two Enterotoxigenic Escherichia coli (ETEC) Fimbrial Multiepitope Fusion Antigens Induces the Production of Neutralizing Antibodies against Five ETEC Fimbriae (F4, F5, F6, F18, and F41)

Duan

Pang

et al. 2020

Appl Environ Microbiol

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Fimbriae mediate the initial adherence of ETEC to the piglet small intestine and play an important role in development of ETEC-driven post-weaning diarrhea (PWD). PWD inflicts huge economic losses on the swine industry each year, making development of alternative treatment and prevention measures for PWD essential. Vaccine candidates that induce anti-fimbriae antibodies that block the initial attachment and colonization of ETEC pathogens with fimbriae are one approach that could help prevent PWD. In this study, we constructed two multi-epitope fusion antigens (MEFAs) that carried, expressed, and displayed representative epitopes of F4, F5, F6, F18 and F41 ETEC fimbriae. These MEFAs used either the F4 major subunit FaeG or the F18 adhesive subunit FedF as a backbone. To assess the potential of these MEFAs as anti-fimbriae vaccine candidates that could help prevent PWD, we generated computational models of the MEFAs, constructed them, and then tested their immunogenicity by using them to immunize mice. Computational modeling showed that all relevant epitopes were exposed on the MEFA surface. We found that co-administration of our MEFAs in mice successfully induced five fimbriae specific antibodies in accordance with the epitopes included in the MEFA constructs. Furthermore, the induced antibodies can significantly inhibit the ability of ETEC strains that express F4, F5, F6, F18, and F41 fimbriae adhere to piglet small intestinal IPEC-1 and IPEC-J2 cells. Our findings indicate that the anti-fimbriae antibodies induced by our FaeG-Fim41a-FanC-FasA and FedF-FasA-Fim41a-FanC fimbriae MEFAs blocked adherence of five ETEC fimbriae, suggesting these multivalent fimbriae MEFAs may be useful for developing broadly protective anti-fimbriae vaccines against PWD caused by ETEC infections. Importance Enterotoxigenic Escherichia coli (ETEC)-associated post-weaning diarrhea (PWD) is still a leading disease in recently weaned piglets. Vaccination is considered to be the most ideal and efficacious strategy for preventing PWD. Recently, a commercialized live monovalent F4 oral vaccine and a bivalent F4/F18 oral vaccine have been demonstrated to effectively protect piglets in the F4+ and F18+ ETEC challenge models. However, they will not provide cross-protection against F5+, F6+, or F41+ ETEC-associated PWD cases due to lack of expressing these fimbriae antigens. Thus, a multivalent vaccine containing all ETEC five fimbriae would be more effective in preventing against ETEC-driven PWD. In this study, we designed two fimbriae-targeted MEFAs using the MEFA technology, further study demonstrated co-administrated these MEFAs in mice can induced protective antibodies against five fimbriae expressed by ETEC. These MEFAs could be used as an efficient PWD vaccine candidate, furthermore, MEFA-based structural technology provides an alternative and promising strategy for the development of vaccines against pathogens with heterogeneous virulence factors.

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Immunogenicity and protective efficacy of a single-dose live non-pathogenic Escherichia coli oral vaccine against F4-positive enterotoxigenic Escherichia coli challenge in pigs

Cited by 46 publications

References 28 publications

Intestinal challenge with enterotoxigenic Escherichia coli in pigs, and nutritional intervention to prevent postweaning diarrhea

Intestinal challenge with enterotoxigenic Escherichia coli in pigs, and nutritional intervention to prevent postweaning diarrhea

Maternal Vaccination. Immunization of Sows during Pregnancy against ETEC Infections

Coimmunization with Two Enterotoxigenic Escherichia coli (ETEC) Fimbrial Multiepitope Fusion Antigens Induces the Production of Neutralizing Antibodies against Five ETEC Fimbriae (F4, F5, F6, F18, and F41)

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