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

Vaccine ◽  
2017 ◽  
Vol 35 (2) ◽  
pp. 353-360 ◽  
Author(s):  
John Morris Fairbrother ◽  
Éric Nadeau ◽  
Louise Bélanger ◽  
Cindy-Love Tremblay ◽  
Danielle Tremblay ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Single Dose ◽  
Protective Efficacy ◽  
Oral Vaccine ◽  
Enterotoxigenic Escherichia Coli ◽  
Pathogenic Escherichia Coli

scholarly journals Immunogenicity and protective efficacy of enterotoxigenic Escherichia coli (ETEC) total RNA against ETEC challenge in a mouse model

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mandi Liu ◽  
Yue Zhang ◽  
Di Zhang ◽  
Yun Bai ◽  
Guomei Liu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Mouse Model ◽  
Immune Responses ◽  
Protective Efficacy ◽  
Enterotoxigenic Escherichia Coli ◽  
Economic Losses ◽  
Th2 Response ◽  
Total Rna ◽  
Etec Infection

AbstractEnterotoxigenic Escherichia coli (ETEC), an essential cause of post-weaning diarrhea (PWD) in piglets, leads to significant economic losses to the pig industry. The present study aims to identify the role of ETEC total RNA in eliciting immune responses to protect animals against ETEC infection. The results showed that the total RNA isolated from pig-derived ETEC K88ac strain effectively stimulated the IL-1β secretion of porcine intestinal epithelial cells (IPEC-J2). The mouse model immunized with ETEC total RNA via intramuscular injection (IM) or oral route (OR) was used to evaluate the protective efficiency of the ETEC total RNA. The results suggested that 70 μg ETEC total RNA administered by either route significantly promoted the production of the serum IL-1β and K88ac specific immunoglobulins (IgG, IgM, and IgA). Besides, the ETEC RNA administration augmented strong mucosal immunity by elevating K88ac specific IgA level in the intestinal fluid. Intramuscularly administered RNA induced a Th1/Th2 shift toward a Th2 response, while the orally administered RNA did not. The ETEC total RNA efficiently protected the animals against the ETEC challenge either by itself or as an adjuvant. The histology characterization of the small intestines also suggested the ETEC RNA administration protected the small intestinal structure against the ETEC infection. Particularly of note was that the immunity level and protective efficacy caused by ETEC RNA were dose-dependent. These findings will help understand the role of bacterial RNA in eliciting immune responses, and benefit the development of RNA-based vaccines or adjuvants.

scholarly journals Protective Passive Immunity in Escherichia coli ETEC-Challenged Neonatal Mice Conferred by Orally Immunized Dams with Nanoparticles Containing Homologous Outer Membrane Vesicles

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 286
Author(s):  
Jose Matías ◽  
Yadira Pastor ◽  
Juan M. Irache ◽  
Carlos Gamazo
Keyword(s):  
Escherichia Coli ◽  
Single Dose ◽  
Outer Membrane ◽  
Passive Immunization ◽  
Membrane Vesicles ◽  
Oral Immunization ◽  
Outer Membrane Vesicles ◽  
Enterotoxigenic Escherichia Coli ◽  
Human Beings ◽  
Polymer Conjugate

Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of illness and death in mammals, including neonatal, recently weaned pigs and infant human beings. We have previously shown that outer membrane vesicles (OMV) obtained from ETEC serotypes encapsulated into zein nanoparticles, coated with a Gantrez-mannosamine polymer conjugate (OMV-NP), were immunogenic in mice and sows. In the present study, we show that pups from vaccinated mice were protected against ETEC F4 serotype challenge through maternal passive immunization. OMV from F4 cultures were collected and characterized. Two-week-pregnant BALB/c mice were orally immunized with a single dose of vesicles (0.2 mg) either free (OMV) or encapsulated into nanoparticles (OMV-NP). Evaluation of the antibodies in serum (IgG1, Ig2a or IgA) and feces (IgA) of dams immunized with OMV-NP revealed an enhancement of specific immunogenicity. The antibody response conferred by the nanoparticle adjuvant was also correlated with IL-6 and IL-10 splenic levels. Each mother was allowed to feed her progeny for one week. Suckling pups presented specific IgA in feces demonstrating their passive immunization through colostrum intake. Two weeks after the pups were born, they were infected orally with a single dose of F4 E. coli (1.2 × 108 CFU/pup). Results showed that 70% of the pups from dams immunized with OMV-NP were protected. In contrast, 80% of the pups from dams immunized with free OMV died as a result of the experimental challenge. These findings support the use of zein nanoparticles coated with a Gantrez-mannosamine shield as adjuvant delivery system for the oral immunization during pregnancy to confer immunity to the offspring through maternal immunization

Towards a live oral vaccine against enterotoxigenic Escherichia coli of swine

Vaccine ◽  
1988 ◽  
Vol 6 (5) ◽  
pp. 387-389 ◽  
Author(s):  
Stephen Attridge ◽  
Jim Hackett ◽  
Renato Morona ◽  
Peter Whyte
Keyword(s):  
Escherichia Coli ◽  
Oral Vaccine ◽  
Enterotoxigenic Escherichia Coli ◽  
Live Oral Vaccine

scholarly journals Immunogenicity and Protective Efficacy against Enterotoxigenic Escherichia coli Colonization following Intradermal, Sublingual, or Oral Vaccination with EtpA Adhesin

2016 ◽  
Vol 23 (7) ◽  
pp. 628-637 ◽  
Author(s):  
Qingwei Luo ◽  
Tim J. Vickers ◽  
James M. Fleckenstein
Keyword(s):  
Escherichia Coli ◽  
Vaccine Development ◽  
Protective Antigen ◽  
Protective Efficacy ◽  
Enterotoxigenic Escherichia Coli ◽  
Oral Vaccination ◽  
Content Type ◽  
Degree Of Protection ◽  
Alternative Routes

EnterotoxigenicEscherichia coli(ETEC) strains are a common cause of diarrhea. Extraordinary antigenic diversity has prompted a search for conserved antigens to complement canonical approaches to ETEC vaccine development. EtpA, an immunogenic extracellular ETEC adhesin relatively conserved in the ETEC pathovar, has previously been shown to be a protective antigen following intranasal immunization. These studies were undertaken to explore alternative routes of EtpA vaccination that would permit use of a double mutant (R192G L211A) heat-labile toxin (dmLT) adjuvant. Here, oral vaccination with EtpA adjuvanted with dmLT afforded significant protection against small intestinal colonization, and the degree of protection correlated with fecal IgG, IgA, or total fecal antibody responses to EtpA. Sublingual vaccination yielded compartmentalized mucosal immune responses with significant increases in anti-EtpA fecal IgG and IgA, and mice vaccinated via this route were also protected against colonization. In contrast, while intradermal (i.d.) vaccination achieved high levels of both serum and fecal antibodies against both EtpA and dmLT, mice vaccinated via the i.d. route were not protected against subsequent colonization and the avidity of serum IgG and IgA EtpA-specific antibodies was significantly lower after i.d. immunization compared to other routes. Finally, we demonstrate that antiserum from vaccinated mice significantly impairs binding of LT to cognate GM1 receptors and shows near complete neutralization of toxin delivery by ETECin vitro. Collectively, these data provide further evidence that EtpA could complement future vaccine strategies but also suggest that additional effort will be required to optimize its use as a protective immunogen.

scholarly journals Experimental Infection of Human Volunteers with the Heat-Stable Enterotoxin-Producing Enterotoxigenic Escherichia coli Strain TW11681

Pathogens ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 84 ◽  
Author(s):  
Sunniva Todnem Sakkestad ◽  
Hans Steinsland ◽  
Steinar Skrede ◽  
Elisabeth Kleppa ◽  
Kristine Lillebø ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
T Cell ◽  
Protective Efficacy ◽  
T Cell Responses ◽  
Enterotoxigenic Escherichia Coli ◽  
Cd4 T Cell ◽  
Infection Model ◽  
Serological Response ◽  
Cell Responses ◽  
Heat Stable

Infection with enterotoxigenic Escherichia coli (ETEC) producing the heat-stable enterotoxin (ST) is one of the most important causes of childhood diarrhoea in low- and middle-income countries. Here, we undertook a controlled human infection model (CHIM) study to investigate whether ST-producing ETEC strain TW11681 would be suitable for testing the protective efficacy of new ST-based vaccine candidates in vaccine challenge models. In groups of three, nine volunteers ingested 1 × 106, 1 × 107, or 1 × 108 colony-forming units (CFU) of TW11681. Flow cytometry-based assays were used to measure CD4+ T cell responses and antibody levels targeting virulence factors expressed by the strain. We found that infection with TW11681 elicited few and mild symptoms, including mild diarrhoea in two volunteers, both of whom ingested 1 × 106 CFU. Averaged across all volunteers, the CD4+ T cell responses specific for E. coli YghJ mucinase peaked 10 days after infection (3.2-fold (p = 0.016)), while the CD4+ T cell responses specific for Colonization Factor Antigen I (CFA/I) major fimbrial subunit (CfaB) peaked after 28 days (3.6-fold (p = 0.063)). The serum CfaB-specific anti-IgA and anti-IgG/IgM levels were significantly increased and peaked 3 months after infection. Both remained elevated for the duration of the 12-month follow-up. The corresponding anti-YghJ serological response was strongest after 10 days, although a significant increase was seen only for IgA levels (3.2-fold (p = 0.008)). In conclusion, due to its low diarrhoea attack risk, TW11681 is probably not suitable for testing the efficacy of new vaccines in human challenge studies at doses 1 × 106 to 1 × 108. However, the strain may still be useful in CHIMs for studying ETEC host-pathogen interactions.

scholarly journals Attenuated Shigella flexneri 2a Vaccine Strain CVD 1204 Expressing Colonization Factor Antigen I and Mutant Heat-Labile Enterotoxin of Enterotoxigenic Escherichia coli

2000 ◽  
Vol 68 (9) ◽  
pp. 4884-4892 ◽  
Author(s):  
Hilary Koprowski ◽  
Myron M. Levine ◽  
Richard J. Anderson ◽  
Genevieve Losonsky ◽  
Mariagrazia Pizza ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Vaccine Strain ◽  
Guinea Pigs ◽  
Oral Vaccine ◽  
Shigella Flexneri ◽  
Surface Expression ◽  
Enterotoxigenic Escherichia Coli ◽  
Secretory Iga ◽  
Colonization Factor ◽  
Heat Labile

ABSTRACT A multivalent live oral vaccine against both Shigellaspp. and enterotoxigenic Escherichia coli (ETEC) is being developed based on the hypothesis that protection can be achieved if attenuated shigellae express ETEC fimbrial colonization factors and genetically detoxified heat-labile toxin from a human ETEC isolate (LTh). Two detoxified derivatives of LTh, LThK63 and LThR72, were engineered by substitution—serine to lysine at residue 63, or lysine to arginine at residue 72. The genes encoding these two derivatives were cloned separately on expression plasmids downstream from the CFA/I operon. Following electroporation into S. flexneri 2a vaccine strain CVD 1204, coexpression of CFA/I and LThK63 or LThR72 was demonstrated by Western blot analysis, GM1 binding assays, and agglutination with anti-CFA/I antiserum. Hemagglutination and electron microscopy confirmed surface expression of CFA/I. Guinea pigs immunized intranasally on days 0 and 15 with CVD 1204 expressing CFA/I and LThK63 or LThR72 exhibited high titers of both serum immunoglobulin G (IgG) and mucosal secretory IgA anti-CFA/I; 40% of the animals produced antibodies directed against LTh. All immunized guinea pigs also produced mucosal IgA (in tears) and serum IgG anti-S. flexneri 2a O antibodies. Furthermore, all immunized animals were protected from challenge with wild-type S. flexneri 2a. This prototype Shigella-ETEC hybrid vaccine demonstrates the feasibility of expressing multiple ETEC antigens on a single plasmid in an attenuated Shigella vaccine strain and engendering immune responses against both the heterologous antigens and vector strain.

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