Protective efficacy and immunogenicity of Escherichia coli K13 diphtheria toxoid conjugate against experimental ascending pyelonephritis

Kumar, Varinder; Nk, Ganguly; Joshi, Kusum; Mittal, Rahul; Harjai, Kusum; Chhibber, Sanjay; Sharma, Shaveta

doi:10.1007/s00430-005-0241-x

Cited by 8 publications

(6 citation statements)

References 37 publications

(34 reference statements)

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“…• Heterogeneity of the proteins of the bacterial membrane Targeting capsule (Kaijser et al, 1983;Roberts et al, 1993;Kumar et al, 2005;Stenutz et al, 2006) • Promising animal model results…”

Section: Vaccinementioning

confidence: 99%

Alternative Therapeutic Options to Antibiotics for the Treatment of Urinary Tract Infections

et al. 2020

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Urinary tract infections (UTIs) mainly caused by Uropathogenic Escherichia coli (UPEC), are common bacterial infections. Many individuals suffer from chronically recurring UTIs, sometimes requiring long-term prophylactic antibiotic regimens. The global emergence of multi-drug resistant uropathogens in the last decade underlines the need for alternative non-antibiotic therapeutic and preventative strategies against UTIs. The research on non-antibiotic therapeutic options in UTIs has focused on the following phases of the pathogenesis: colonization, adherence of pathogens to uroepithelial cell receptors and invasion. In this review, we discuss vaccines, small compounds, nutraceuticals, immunomodulating agents, probiotics and bacteriophages, highlighting the challenges each of these approaches face. Most of these treatments show interesting but only preliminary results. Lactobacillus-containing products and cranberry products in conjunction with propolis have shown the most robust results to date and appear to be the most promising new alternative to currently used antibiotics. Larger efficacy clinical trials as well as studies on the interplay between non-antibiotic therapies, uropathogens and the host immune system are warranted.

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Section: Vaccinementioning

confidence: 99%

Alternative Therapeutic Options to Antibiotics for the Treatment of Urinary Tract Infections

et al. 2020

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“…For example, immunization with the type 1 fimbrial adhesin, FimH, conjugated to its periplasmic chaperone, FimC, reduced murine bladder colonization by 99.9%, as well as provided protection in a primate model [14],[15]. Additionally, subunit vaccines based on several other surface-exposed molecules such as P fimbriae (PapDG complex), alpha hemolysin, Dr fimbriae, the salmochelin receptor IroN, and a conjugation of capsule polysaccharide K13 with diphtheria toxoid have been shown to induce at least some immune response in immunized animals [16]–[20]. However, although much research has focused on the development of a vaccine against UPEC, none are available in the United States.…”

Section: Introductionmentioning

confidence: 99%

Mucosal Immunization with Iron Receptor Antigens Protects against Urinary Tract Infection

et al. 2009

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Uncomplicated infections of the urinary tract, caused by uropathogenic Escherichia coli, are among the most common diseases requiring medical intervention. A preventive vaccine to reduce the morbidity and fiscal burden these infections have upon the healthcare system would be beneficial. Here, we describe the results of a large-scale selection process that incorporates bioinformatic, genomic, transcriptomic, and proteomic screens to identify six vaccine candidates from the 5379 predicted proteins encoded by uropathogenic E. coli strain CFT073. The vaccine candidates, ChuA, Hma, Iha, IreA, IroN, and IutA, all belong to a functional class of molecules that is involved in iron acquisition, a process critical for pathogenesis in all microbes. Intranasal immunization of CBA/J mice with these outer membrane iron receptors elicited a systemic and mucosal immune response that included the production of antigen-specific IgM, IgG, and IgA antibodies. The cellular response to vaccination was characterized by the induction and secretion of IFN-γ and IL-17. Of the six potential vaccine candidates, IreA, Hma, and IutA provided significant protection from experimental infection. In immunized animals, class-switching from IgM to IgG and production of antigen-specific IgA in the urine represent immunological correlates of protection from E. coli bladder colonization. These findings are an important first step toward the development of a subunit vaccine to prevent urinary tract infections and demonstrate how targeting an entire class of molecules that are collectively required for pathogenesis may represent a fundamental strategy to combat infections.

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“…Purified E coli K13 polysaccharide conjugated to bovine serum albumin protected rats from pyelonephritis (299). A different group conjugated E. coli K13 to diphtheria toxoid and found that the vaccine decreased renal bacteria load and disease severity scores in mice after challenge with a K13 UPEC strain (300). A considerable challenge in formulating a vaccine targeting capsule or O antigen, the most exposed component of LPS, is the fact that there is a great heterogeneity of serotypes among E. coli isolates.…”

Section: Uti Vaccinesmentioning

confidence: 99%

Drug and Vaccine Development for the Treatment and Prevention of Urinary Tract Infections

O’Brien¹,

Hannan

Nielsen³

et al. 2016

Microbiol Spectr

110

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Urinary tract infections (UTI) are among the most common bacterial infections in humans, affecting millions of people every year. UTI cause significant morbidity in women throughout their lifespan, in infant boys, in older men, in individuals with underlying urinary tract abnormalities, and in those that require long-term urethral catheterization, such as patients with spinal cord injuries or incapacitated individuals living in nursing homes. Serious sequelae include frequent recurrences, pyelonephritis with sepsis, renal damage in young children, pre-term birth, and complications of frequent antimicrobial use including high-level antibiotic resistance and Clostridium difficile colitis. Uropathogenic E. coli (UPEC) cause the vast majority of UTI, but less common pathogens such as Enterococcus faecalis and other enterococci frequently take advantage of an abnormal or catheterized urinary tract to cause opportunistic infections. While antibiotic therapy has historically been very successful in controlling UTI, the high rate of recurrence remains a major problem, and many individuals suffer from chronically recurring UTI, requiring long-term prophylactic antibiotic regimens to prevent recurrent UTI. Furthermore, the global emergence of multi-drug resistant UPEC in the past ten years spotlights the need for alternative therapeutic and preventative strategies to combat UTI, including anti-infective drug therapies and vaccines. In this chapter, we review recent advances in the field of UTI pathogenesis, with an emphasis on the identification of promising drug and vaccine targets. We then discuss the development of new UTI drugs and vaccines, highlighting the challenges these approaches face and the need for a greater understanding of urinary tract mucosal immunity.

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Protective efficacy and immunogenicity of Escherichia coli K13 diphtheria toxoid conjugate against experimental ascending pyelonephritis

Cited by 8 publications

References 37 publications

Alternative Therapeutic Options to Antibiotics for the Treatment of Urinary Tract Infections

Alternative Therapeutic Options to Antibiotics for the Treatment of Urinary Tract Infections

Mucosal Immunization with Iron Receptor Antigens Protects against Urinary Tract Infection

Drug and Vaccine Development for the Treatment and Prevention of Urinary Tract Infections

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