Clinical trial to evaluate safety and immunogenicity of an oral inactivated enterotoxigenic Escherichia coli prototype vaccine containing CFA/I overexpressing bacteria and recombinantly produced LTB/CTB hybrid protein

Lundgren, Anna; Leach, Susannah; Tobias, Joshua; Carlin, Nils; Gustafsson, Björn; Jertborn, Marianne; Bourgeois, Louis; Walker, Richard I.; Holmgren, Jan; Svennerholm, Ann‐Mari

doi:10.1016/j.vaccine.2012.12.063

Cited by 48 publications

(49 citation statements)

References 30 publications

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“…Overexpression of various CFs and hybrid CFs in a murine model showed an immune response to the CFs that was higher than that for reference ETEC strains (781)(782)(783)(784). A recent publication described a phase 1 trial in volunteers using an E. coli strain overexpressing CFA/I coupled with a hybrid LT and CT (LCTBA) and demonstrated that it was safe and elicited an antibody response to both LTB and CFA/I (785).…”

Section: Clinical Considerationsmentioning

confidence: 99%

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

et al. 2013

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SUMMARY Although Escherichia coli can be an innocuous resident of the gastrointestinal tract, it also has the pathogenic capacity to cause significant diarrheal and extraintestinal diseases. Pathogenic variants of E. coli (pathovars or pathotypes) cause much morbidity and mortality worldwide. Consequently, pathogenic E. coli is widely studied in humans, animals, food, and the environment. While there are many common features that these pathotypes employ to colonize the intestinal mucosa and cause disease, the course, onset, and complications vary significantly. Outbreaks are common in developed and developing countries, and they sometimes have fatal consequences. Many of these pathotypes are a major public health concern as they have low infectious doses and are transmitted through ubiquitous mediums, including food and water. The seriousness of pathogenic E. coli is exemplified by dedicated national and international surveillance programs that monitor and track outbreaks; unfortunately, this surveillance is often lacking in developing countries. While not all pathotypes carry the same public health profile, they all carry an enormous potential to cause disease and continue to present challenges to human health. This comprehensive review highlights recent advances in our understanding of the intestinal pathotypes of E. coli .

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Section: Clinical Considerationsmentioning

confidence: 99%

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

et al. 2013

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“…The over-expression of ETEC antigens by non-pathogenic E. coli is one strategy which has delivered promising pre-clinical and phase I human trial results [101][102][103]. Additionally, novel strains of V. cholerae expressing multiple surface antigens have been generated and hold promise for future trials [104].…”

Section: Classes Of Mucosal Antigenmentioning

confidence: 99%

Delivery strategies to enhance oral vaccination against enteric infections

Davitt

Lavelle

2015

Advanced Drug Delivery Reviews

131

102

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“…LT and LT-like vaccines have been shown to confer protection but are hampered by limited coverage and durability (12)(13)(14). New whole-cell live and inactivated vaccines containing both fimbriae and LT-based components are currently in clinical evaluation (17)(18)(19). Elucidation of the structure and function of CFA/I fimbriae suggests an alternative approach that targets the tip-localized adhesin to more specifically elicit antiadhesive immunity to abrogate the initial step of ETEC colonization.…”

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confidence: 99%

Maternal Vaccination with a Fimbrial Tip Adhesin and Passive Protection of Neonatal Mice against Lethal Human Enterotoxigenic Escherichia coli Challenge

et al. 2015

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e Globally, enterotoxigenic Escherichia coli (ETEC) is a leading cause of childhood and travelers' diarrhea, for which an effective vaccine is needed. Prevalent intestinal colonization factors (CFs) such as CFA/I fimbriae and heat-labile enterotoxin (LT) are important virulence factors and protective antigens. We tested the hypothesis that donor strand-complemented CfaE (dscCfaE), a stabilized form of the CFA/I fimbrial tip adhesin, is a protective antigen, using a lethal neonatal mouse ETEC challenge model and passive dam vaccination. For CFA/I-ETEC strain H10407, which has been extensively studied in volunteers, an inoculum of 2 ؋ 10 7 bacteria resulted in 50% lethal doses (LD 50 ) in neonatal DBA/2 mice. Vaccination of female DBA/2 mice with CFA/I fimbriae or dscCfaE, each given with a genetically attenuated LT adjuvant (LTK63) by intranasal or orogastric delivery, induced high antigen-specific serum IgG and fecal IgA titers and detectable milk IgA responses. Neonates born to and suckled by dams antenatally vaccinated with each of these four regimens showed 78 to 93% survival after a 20؋ LD 50 challenge with H10407, compared to 100% mortality in pups from dams vaccinated with sham vaccine or LTK63 only. Crossover experiments showed that high pup survival rates after ETEC challenge were associated with suckling but not birthing from vaccinated dams, suggesting that vaccine-specific milk antibodies are protective. In corroboration, preincubation of the ETEC inoculum with antiadhesin and antifimbrial bovine colostral antibodies conferred a dose-dependent increase in pup survival after challenge. These findings indicate that the dscCfaE fimbrial tip adhesin serves as a protective passive vaccine antigen in this small animal model and merits further evaluation.

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Clinical trial to evaluate safety and immunogenicity of an oral inactivated enterotoxigenic Escherichia coli prototype vaccine containing CFA/I overexpressing bacteria and recombinantly produced LTB/CTB hybrid protein

Cited by 48 publications

References 30 publications

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

Recent Advances in Understanding Enteric Pathogenic Escherichia coli

Delivery strategies to enhance oral vaccination against enteric infections

Maternal Vaccination with a Fimbrial Tip Adhesin and Passive Protection of Neonatal Mice against Lethal Human Enterotoxigenic Escherichia coli Challenge

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