06 / THE GLOBAL BURDEN OF SHIGELLA AND ENTEROTOXIGENIC E. COLI: A CALL FOR THE NEED OF ACCELERATING VACCINE DEVELOPMENT EFFORTS

2018 ◽  
Author(s):  
Ibrahim Khalil
Keyword(s):  
Vaccine Development ◽  
Global Burden ◽  
E Coli

scholarly journals Cervical cancer vaccine development

Sexual Health ◽  
2010 ◽  
Vol 7 (3) ◽  
pp. 230 ◽  
Author(s):  
Ian H. Frazer
Keyword(s):  
Cervical Cancer ◽  
Clinical Trials ◽  
Human Papillomavirus ◽  
Cancer Vaccine ◽  
Vaccine Development ◽  
Global Burden ◽  
Viral Capsids ◽  
Cervical Epithelium ◽  
Papillomavirus Vaccines ◽  
Cervical Cancer Vaccine

Cervical cancer is initiated by infection of cervical epithelium with human papillomavirus. Vaccines have been developed, incorporating papillomavirus viral capsids and alum based adjuvants. In extensive clinical trials these vaccines have been shown safe and effective in preventing infection with, and disease caused by, the papillomavirus genotypes they incorporate, in women not already infected. These vaccines have the potential to reduce the global burden of cervical cancer by up to 70%.

Ability ofEscherichia coliO157:H7 isolates to colonize the intestinal tract of conventional adult CD1 mice is transient

2001 ◽  
Vol 47 (1) ◽  
pp. 91-95 ◽  
Author(s):  
J Wayne Conlan ◽  
Sonia L Bardy ◽  
Rhonda KuoLee ◽  
Ann Webb ◽  
Malcolm B Perry
Keyword(s):  
Escherichia Coli ◽  
Mouse Model ◽  
Intestinal Tract ◽  
Vaccine Development ◽  
Escherichia Coli O157 ◽  
Intestinal Colonization ◽  
E Coli ◽  
Cd1 Mice ◽  
A Current

In an attempt to improve upon a current mouse model of intestinal colonization by Escherichia coli O157:H7 used in this laboratory for vaccine development, nine clinical isolates of the pathogen were screened for their ability to persist in the intestinal tract of conventional adult CD-1 mice. None of the test isolates of E. coli O157:H7 were capable of colonizing these mice for a period of more than two weeks. Most of the isolates appeared to be benign for the experimental host, but one isolate was lethal. This virulence correlated with the ability of the latter isolate to produce large quantities of Shiga-like toxin 2 in vitro.

scholarly journals Identification of lipid A deacylase as a novel, highly conserved and protective antigen against enterohemorrhagic Escherichia coli

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Maricarmen Rojas-Lopez ◽  
Manuele Martinelli ◽  
Valentina Brandi ◽  
Grégory Jubelin ◽  
Fabio Polticelli ◽  
...  
Keyword(s):  
Lipid A ◽  
Vaccine Development ◽  
Protective Antigen ◽  
Vaccine Candidate ◽  
Bacterial Load ◽  
Enterohemorrhagic Escherichia Coli ◽  
Protein Antigens ◽  
E Coli ◽  
Epidemiology Data ◽  
Potential Vaccine

AbstractEnterohemorrhagic E. coli (EHEC) is a major cause of large outbreaks worldwide associated with hemorrhagic colitis and hemolytic uremic syndrome. While vaccine development is warranted, a licensed vaccine, specific for human use, against EHEC is not yet available. In this study, the reverse vaccinology approach combined with genomic, transcriptional and molecular epidemiology data was applied on the EHEC O157:H7 genome to select new potential vaccine candidates. Twenty-four potential protein antigens were identified and one of them (MC001) was successfully expressed onto Generalized Modules for Membrane Antigens (GMMA) delivery system. GMMA expressing this vaccine candidate was immunogenic, raising a specific antibody response. Immunization with the MC001 candidate was able to reduce the bacterial load of EHEC O157:H7 strain in feces, colon and caecum tissues after murine infection. MC001 is homologue to lipid A deacylase enzyme (LpxR), and to our knowledge, this is the first study describing it as a potential vaccine candidate. Gene distribution and sequence variability analysis showed that MC001 is present and conserved in EHEC and in enteropathogenic E. coli (EPEC) strains. Given the high genetic variability among and within E. coli pathotypes, the identification of such conserved antigen suggests that its inclusion in a vaccine might represent a solution against major intestinal pathogenic strains.

scholarly journals The Intriguing Interaction of Escherichia coli with the Host Environment and Innovative Strategies To Interfere with Colonization: a Summary of the 2019 E. coli and the Mucosal Immune System Meeting

2020 ◽  
Vol 86 (24) ◽  
Author(s):  
Eric Cox ◽  
Meryem Aloulou ◽  
James M. Fleckenstein ◽  
Christina Schäffer ◽  
Åsa Sjöling ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Immune System ◽  
Vaccine Development ◽  
Animal Health ◽  
Mucosal Immune System ◽  
Periodontal Pathogen ◽  
Content Type ◽  
Innovative Strategies ◽  
E Coli ◽  
Health And Disease

ABSTRACT The third E. coli and the Mucosal Immune System (ECMIS) meeting was held at Ghent University in Belgium from 2 to 5 June 2019. It brought together an international group of scientists interested in mechanisms of colonization, host response, and vaccine development. ECMIS distinguishes itself from related meetings on these enteropathogens by providing a greater emphasis on animal health and disease and covering a broad range of pathotypes, including enterohemorrhagic, enteropathogenic, enterotoxigenic, enteroaggregative, and extraintestinal pathogenic Escherichia coli. As it is well established that the genus Shigella represents a subspecies of E. coli, these organisms along with related enteroinvasive E. coli are also included. In addition, Tannerella forsythia, a periodontal pathogen, was presented as an example of a pathogen which uses its surface glycans for mucosal interaction. This review summarizes several highlights from the 2019 meeting and major advances to our understanding of the biology of these pathogens and their impact on the host.

scholarly journals Enhanced Prokaryotic Expression of Dengue Virus Envelope Protein

2013 ◽  
Vol 16 (4) ◽  
pp. 609 ◽  
Author(s):  
Advaita Ganguly ◽  
Ravindra B. Malabadi ◽  
Dipankar Das ◽  
Mavanur R. Suresh ◽  
Hoon H Sunwoo
Keyword(s):  
Dengue Virus ◽  
Envelope Protein ◽  
Vaccine Development ◽  
Virus Envelope ◽  
E Coli ◽  
C Terminus ◽  
Virus Envelope Protein ◽  
Biological Functionality ◽  
Dengue Diagnostics

Purpose. To highlight the expression and purification of the recombinant dengue virus type-1 antigen exploiting the codon optimized full length envelope for increased yield in E. coli. Methods. A 6x His tag was inserted at the C terminus to facilitate purification. The purified protein was recognized in Western blot by Monoclonal antibody specific for the tag. The in vitro refolded recombinant protein was used to immunize mice for the development of hybridomas and also analyzed for its biological functionality with heparan sulfate binding assay. Results. The polyclonal anti-sera from the immunized mice were found to recognize the envelope protein thereby establishing the immunogenicity of the protein. Conclusion. The purified envelope protein could potentially be used towards dengue diagnostics and vaccine development efforts. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

scholarly journals Use of In Vivo-Induced Antigen Technology for Identification of Escherichia coli O157:H7 Proteins Expressed during Human Infection

2005 ◽  
Vol 73 (5) ◽  
pp. 2665-2679 ◽  
Author(s):  
Manohar John ◽  
Indira T. Kudva ◽  
Robert W. Griffin ◽  
Allen W. Dodson ◽  
Bethany McManus ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Vaccine Development ◽  
Human Infection ◽  
Escherichia Coli O157 ◽  
Standard Laboratory ◽  
E Coli ◽  
Phase Culture ◽  
Stool Specimens

ABSTRACT Using in vivo-induced antigen technology (IVIAT), a modified immunoscreening technique that circumvents the need for animal models, we directly identified immunogenic Escherichia coli O157:H7 (O157) proteins expressed either specifically during human infection but not during growth under standard laboratory conditions or at significantly higher levels in vivo than in vitro. IVIAT identified 223 O157 proteins expressed during human infection, several of which were unique to this study. These in vivo-induced (ivi) proteins, encoded by ivi genes, mapped to the backbone, O islands (OIs), and pO157. Lack of in vitro expression of O157-specific ivi proteins was confirmed by proteomic analysis of a mid-exponential-phase culture of E. coli O157 grown in LB broth. Because ivi proteins are expressed in response to specific cues during infection and might help pathogens adapt to and counter hostile in vivo environments, those identified in this study are potential targets for drug and vaccine development. Also, such proteins may be exploited as markers of O157 infection in stool specimens.

scholarly journals Preclinical characterization of immunogenicity and efficacy against diarrhea from MecVax, a multivalent enterotoxigenic E. coli vaccine candidate

2021 ◽  
Author(s):  
Hyesuk Seo ◽  
Carolina Garcia ◽  
Xiaosai Ruan ◽  
Qiangde Duan ◽  
David A Sack ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Developing Countries ◽  
Vaccine Development ◽  
Vaccine Candidate ◽  
Preclinical Study ◽  
Watery Diarrhea ◽  
E Coli ◽  
Heat Stable ◽  
Protective Antibodies

There are no vaccines licensed for enterotoxigenic Escherichia coli (ETEC), a leading cause of diarrhea for children in developing countries and international travelers. Virulence heterogeneity among strains and difficulties identifying safe antigens for protective antibodies against STa, a potent but poorly immunogenic heat-stable toxin which plays a key role in ETEC diarrhea, are challenges in ETEC vaccine development. To overcome these challenges, we applied toxoid fusion strategy and novel epitope- and structure-based multiepitope-fusion-antigen (MEFA) vaccinology platform to construct two chimeric multivalent proteins, toxoid fusion 3xSTaN12S-mnLTR192G/L211A and adhesin CFA/I/II/IV MEFA, and demonstrated that proteins induced protective antibodies against STa and heat-labile toxin (LT) produced by all ETEC strains or the seven most important ETEC adhesins (CFA/I, CS1 to CS6) expressed by the ETEC strains causing 60-70% diarrheal cases and moderate-to-severe cases. Combining two proteins, we prepared a protein-based multivalent ETEC vaccine, MecVax. MecVax was broadly immunogenic; mice and pigs intramuscularly immunized with MecVax developed no apparent adverse effects but robust antibody responses to the target toxins and adhesins. Importantly, MecVax-induced antibodies were broadly protective, demonstrated by significant adherence inhibition against E. coli bacteria producing any of the seven adhesins and neutralization of STa and CT enterotoxicity. Moreover, MecVax protected against watery diarrhea, and over 70% or 90% any diarrhea from an STa+ or an LT+ ETEC strain in a pig challenge model. These results indicated that MecVax induces broadly protective antibodies and prevents diarrhea preclinically, signifying MecVax potentially an effective injectable vaccine for ETEC. IMPORTANCE: Enterotoxigenic Escherichia coli (ETEC) bacteria are a top cause of children’s diarrhea and travelers’ diarrhea and are responsible for over 220 million diarrheal cases and more than 100,000 deaths annually. A safe and effective ETEC vaccine can significantly improve public health, particularly in developing countries. Data from this preclinical study showed that MecVax induces broadly protective anti-adhesin and antitoxin antibodies, becoming the first ETEC vaccine candidate to induce protective antibodies inhibiting adherence of the seven most important ETEC adhesins and neutralizing enterotoxicity of LT but also STa toxin. More importantly, MecVax is shown to protect against clinical diarrhea from STa+ or LT+ ETEC infection in a pig challenge model, recording protection from antibodies induced by protein-based injectable subunit vaccine MecVax against ETEC diarrhea and perhaps the possibility of IM administered protein vaccines for protection against intestinal mucosal infection.

scholarly journals Contribution of noncanonical antigens to virulence and adaptive immunity in human infection with enterotoxigenic E. coli

2020 ◽  
Author(s):  
FM Kuhlmann ◽  
RO Laine ◽  
S Afrin ◽  
R Nakajima ◽  
M Akhtar ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Human Infection ◽  
Middle Income ◽  
Symptomatic Disease ◽  
E Coli ◽  
Middle Income Countries ◽  
Colonization Factor ◽  
Specific Antigens ◽  
Colonization Factors

AbstractEnterotoxigenic E. coli (ETEC) contribute significantly to the substantial burden of infectious diarrhea among children living in low and middle income countries. In the absence of a vaccine for ETEC, children succumb to acute dehydration as well as non-diarrheal sequelae related to these infections including malnutrition. The considerable diversity of ETEC genomes has complicated canonical vaccine development approaches focused on a subset of antigens known as colonization factors (CFs). To identify additional conserved immunogens, we mined genomic sequences of 89 ETEC isolates, bioinformatically selected potential surface-exposed pathovar-specific antigens conserved in more than 40% of the genomes (n=118), and assembled the representative proteins onto microarrays, complemented with known or putative colonization factor subunit molecules (n=52), and toxin subunits to interrogate samples from individuals with acute symptomatic ETEC infections. Surprisingly, in this open-aperture approach, we found that immune responses were largely constrained to a small number of antigens including individual colonization factor antigens and EtpA, an extracellular adhesin. In a Bangladeshi cohort of naturally infected children < 2 years of age, both EtpA and a second noncanonical antigen, EatA, elicited significant serologic responses that were associated with protection from symptomatic illness. In addition, children infected with ETEC isolates bearing either etpA or eatA genes were significantly more likely to develop symptomatic disease. These studies support a role for more recently discovered noncanonical antigens in virulence and the development of adaptive immune responses during ETEC infections, findings that may inform vaccine design efforts to complement existing approaches.

scholarly journals Optimised Heterologous Expression and Functional Analysis of the Yersinia pestis F1-Capsular Antigen Regulator Caf1R

2021 ◽  
Vol 22 (18) ◽  
pp. 9805
Author(s):  
Dharmender K. Gahlot ◽  
Gyles Ifill ◽  
Sheila MacIntyre
Keyword(s):  
Yersinia Pestis ◽  
Vaccine Development ◽  
Recombinant Expression ◽  
Bacterial Pathogen ◽  
Clinical Value ◽  
Mobility Shift ◽  
E Coli ◽  
Capsular Antigen ◽  
Mobility Shift Assay

The bacterial pathogen, Yersinia pestis, has caused three historic pandemics and continues to cause small outbreaks worldwide. During infection, Y. pestis assembles a capsule-like protective coat of thin fibres of Caf1 subunits. This F1 capsular antigen has attracted much attention due to its clinical value in plague diagnostics and anti-plague vaccine development. Expression of F1 is tightly regulated by a transcriptional activator, Caf1R, of the AraC/XylS family, proteins notoriously prone to aggregation. Here, we have optimised the recombinant expression of soluble Caf1R. Expression from the native and synthetic codon-optimised caf1R cloned in three different expression plasmids was examined in a library of E. coli host strains. The functionality of His-tagged Caf1R was demonstrated in vivo, but insolubility was a problem with overproduction. High levels of soluble MBP-Caf1R were produced from codon optimised caf1R. Transcriptional-lacZ reporter fusions defined the PM promoter and Caf1R binding site responsible for transcription of the cafMA1 operon. Use of the identified Caf1R binding caf DNA sequence in an electrophoretic mobility shift assay (EMSA) confirmed correct folding and functionality of the Caf1R DNA-binding domain in recombinant MBP-Caf1R. Availability of functional recombinant Caf1R will be a valuable tool to elucidate control of expression of F1 and Caf1R-regulated pathophysiology of Y. pestis.

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