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Danylo Sirskyj, Ashok Kumar, Ali Azizi
Mechanistic details underlying the resulting protective immune response generated by mucosal vaccines remain largely unknown. We investigated the involvement of Toll-like receptor signaling in the induction of humoral immune responses following oral immunization with Dukoral, comparing wild type mice with TLR-2-, TLR-4-, MyD88- and Trif-deficient mice. Although all groups generated similar levels of IgG antibodies, the proliferation of CD4+ T-cells in response to V. cholerae was shown to be mediated via MyD88/TLR signaling, and independently of Trif signaling...
2016: International Journal of Molecular Sciences
Pengpeng Xia, Xianchen Meng, Guoqiang Zhu
Enterotoxigenic Escherichia coli (ETEC) is the most common cause of diarrhea, which is a second leading cause of death for the children under five years old from all over the world. The key factors of ETEC contain both colonization factors (CFs) and enterotoxins including heat-labile enterotoxin (LT) and heat-stable enterotoxin (ST). CFs mediated the binding of bacteria to the host intestinal epithelial cells, whereas LT and ST stimulated the over-secretion of body fluids and electrolytes, resulting in the destruction of the host fluid balance and leading diarrhea...
February 4, 2016: Wei Sheng Wu Xue Bao, Acta Microbiologica Sinica
Hiroshi Izumi, Laurence A Nafie, Rina K Dukor
Searching the 3D structural fragments of organic molecules is challenging because of structural differences between X-ray and theoretically calculated geometries and the conformational flexibility of substituents. The codification program called Conformational Code for Organic Molecules (CCOM) can be used to unambiguously convert 3D conformational data for various molecules to 1D data. Two deviations from Rule E-5.6 of the International Union of Pure and Applied Chemistry (IUPAC) Rules for Nomenclature of Organic Chemistry were introduced to the CCOM program for 3D fragment searching...
May 2016: Chirality
Yingying Duan, Lu Han, Jialiang Zhang, Shunsuke Asahina, Zhehao Huang, Lin Shi, Bo Wang, Yuanyuan Cao, Yuan Yao, Liguo Ma, Cui Wang, Rina K Dukor, Lu Sun, Chun Jiang, Zhiyong Tang, Laurence A Nafie, Shunai Che
Inorganic nanomaterials endowed with hierarchical chirality could open new horizons in physical theory and applications because of their fascinating properties. Here, we report chiral ZnO films coated on quartz substrates with a hierarchical nanostructure ranging from atomic to micrometer scale. Three levels of hierarchical chirality exist in the ZnO films: helical ZnO crystalline structures that form primary helically coiled nanoplates, secondary helical stacking of these nanoplates, and tertiary nanoscale circinate aggregates formed by several stacked nanoplates...
December 7, 2015: Angewandte Chemie
Yeong Ok Baik, Seuk Keun Choi, Remigio M Olveda, Roberto A Espos, Antonio D Ligsay, May B Montellano, Jong Sun Yeam, Jae Seung Yang, Ju Yeon Park, Deok Ryun Kim, Sachin N Desai, Ajit Pal Singh, Ick Young Kim, Chan Wha Kim, Sue-nie Park
BACKGROUND: Currently, there are two oral cholera vaccines (OCV) that are prequalified by the World Health Organization. Both (Dukoral and Shanchol) have been proven to be safe, immunogenic, and effective. As the global supply of OCV remains limited, we assessed the safety and immunogenicity of a new low cost, killed, bivalent OCV (Euvichol) in the Philippines. METHODS: The randomized controlled trial was carried out in healthy Filipino adults and children. Two doses of either the current WHO prequalified OCV (Shanchol) or the same composition OCV being considered for WHO prequalification (Euvichol) were administered to participants...
November 17, 2015: Vaccine
Maruda Shanmugasundaram, Dmitry Kurouski, William Wan, Gerald Stubbs, Rina K Dukor, Laurence A Nafie, Igor K Lednev
Amyloid fibril polymorphism is not well understood despite its potential importance for biological activity and associated toxicity. Controlling the polymorphism of mature fibrils including their morphology and supramolecular chirality by postfibrillation changes in the local environment is the subject of this study. Specifically, the effect of pH on the stability and dynamics of HET-s (218-289) prion fibrils has been determined through the use of vibrational circular dichroism (VCD), deep UV resonance Raman, and fluorescence spectroscopies...
July 9, 2015: Journal of Physical Chemistry. B
Miguel O'Ryan, Roberto Vidal, Felipe del Canto, Juan Carlos Salazar, David Montero
In Part II we discuss the following bacterial pathogens: Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic) and Campylobacter jejuni. In contrast to the enteric viruses and Vibrio cholerae discussed in Part I of this series, for the bacterial pathogens described here there is only one licensed vaccine, developed primarily for Vibrio cholerae and which provides moderate protection against enterotoxigenic E. coli (ETEC) (Dukoral(®)), as well as a few additional candidates in advanced stages of development for ETEC and one candidate for Shigella spp...
2015: Human Vaccines & Immunotherapeutics
Stefan L Karlsson, Elisabeth Ax, Erik Nygren, Susanne Källgård, Margareta Blomquist, Annelie Ekman, John Benktander, Jan Holmgren, Michael Lebens
We describe here the development of stable classical and El Tor V. cholerae O1 strains of the Hikojima serotype that co-express the Inaba and Ogawa antigens of O1 lipopolysaccharide (LPS). Mutation of the wbeT gene reduced LPS perosamine methylation and thereby gave only partial transformation into Ogawa LPS on the cell surface. The strains express approximately equal amounts of Inaba- and Ogawa-LPS antigens which are preserved after formalin-inactivation of the bacteria. Oral immunizations of both inbred and outbred mice with formalin-inactivated whole-cell vaccine preparations of these strains elicited strong intestinal IgA anti-LPS as well as serum vibriocidal antibody responses against both Inaba and Ogawa that were fully comparable to the responses induced by the licensed Dukoral vaccine...
2014: PloS One
Dmitry Kurouski, Joseph D Handen, Rina K Dukor, Laurence A Nafie, Igor K Lednev
The vibrational circular dichroism (VCD) spectra of microcrystals of fibril-forming peptides have been measured for the first time. VCD spectra were measured and compared for microcrystals and fibrils formed from the same peptide, human islet amyloid polypeptide (IAPP, amylin). Structural information related to the supramolecular chirality of both the microcrystals and the fibrils, as well as the VCD enhancement mechanisms in fibrils and microcrystals, is obtained from these spectral comparisons. It is concluded that strongly enhanced VCD does not require braiding of two or more filaments that is permitted in fibrils but not microcrystals...
January 4, 2015: Chemical Communications: Chem Comm
Shahjahan Kabir
Two cholera vaccines, sold as Shanchol and Dukoral, are currently available. This review presents a critical analysis of the protective efficacies of these vaccines. Children under 5 years of age are very vulnerable to cholera and account for the highest incidence of cholera cases and more than half of the resulting deaths. Both Shanchol and Dukoral are two-spaced-dose oral vaccines comprising large numbers of killed cholera bacteria. The former contains Vibrio cholerae O1 and O139 cells, and the latter contains V...
September 2014: Clinical and Vaccine Immunology: CVI
Dmitry Kurouski, Xuefang Lu, Ludmila Popova, William Wan, Maruda Shanmugasundaram, Gerald Stubbs, Rina K Dukor, Igor K Lednev, Laurence A Nafie
The unique enhanced sensitivity of vibrational circular dichroism (VCD) to the formation and development of amyloid fibrils in solution is extended to four additional fibril-forming proteins or peptides where it is shown that the sign of the fibril VCD pattern correlates with the sense of supramolecular filament chirality and, without exception, to the dominant fibril morphology as observed in AFM or SEM images. Previously for insulin, it has been demonstrated that the sign of the VCD band pattern from filament chirality can be controlled by adjusting the pH of the incubating solution, above pH 2 for "normal" left-hand-helical filaments and below pH 2 for "reversed" right-hand-helical filaments...
February 12, 2014: Journal of the American Chemical Society
Aaron M Fleming, Anita M Orendt, Yanan He, Judy Zhu, Rina K Dukor, Cynthia J Burrows
The diastereomeric spiroiminodihydantoin-2'-deoxyribonucleoside (dSp) lesions resulting from 2'-deoxyguanosine (dG) or 8-oxo-7,8-dihydro-2'-deoxyguanosine (dOG) oxidation have generated much attention due to their highly mutagenic nature. Their propeller-like shape leads these molecules to display mutational profiles in vivo that are stereochemically dependent. However, there exist conflicting absolute configuration assignments arising from electronic circular dichroism (ECD) and NOESY-NMR experiments; thus, providing definitive assignments of the 3D structure of these molecules is of great interest...
December 4, 2013: Journal of the American Chemical Society
Atiqur Rahman, Rasheduzzaman Rashu, Taufiqur Rahman Bhuiyan, Fahima Chowdhury, Ashraful Islam Khan, Kamrul Islam, Regina C LaRocque, Edward T Ryan, Jens Wrammert, Stephen B Calderwood, Firdausi Qadri, Jason B Harris
Infection with Vibrio cholerae and oral cholera vaccines (OCVs) induce transient circulating plasmablast responses that peak within approximately 7 days after infection or vaccination. We previously demonstrated that plasmablast responses strongly correlate with subsequent levels of V. cholerae-specific duodenal antibodies up to 6 months after V. cholerae infection. Hence, plasmablast responses provide an early window into the immunologic memory at the mucosal surface. In this study, we characterized plasmablast responses following V...
October 2013: Clinical and Vaccine Immunology: CVI
M Pastor, J L Pedraz, A Esquisabel
Cholera remains a huge public health problem. Although in 1894, the first cholera vaccination was reported, an ideal vaccine that meets all the requirements of the WHO has not yet been produced. Among the different approaches used for cholera vaccination, attenuated vaccines represent a major category; these vaccines are beneficial in being able to induce a strong protective response after a single administration. However, they have possible negative effects on immunocompromised patient populations. Both the licensed CVD103-HgR and other vaccine approaches under development are detailed in this article, such as the Vibrio cholerae 638 vaccine candidate, Peru-15 or CholeraGarde(®) and the VA1...
August 28, 2013: Vaccine
Tanvir Ahmed, Taufiqur R Bhuiyan, K Zaman, David Sinclair, Firdausi Qadri
BACKGROUND: Infection with enterotoxigenic Escherichia coli (ETEC) bacteria is a common cause of diarrhoea in adults and children in developing countries and is a major cause of 'travellers' diarrhoea' in people visiting or returning from endemic regions. A killed whole cell vaccine (Dukoral®), primarily designed and licensed to prevent cholera, has been recommended by some groups to prevent travellers' diarrhoea in people visiting endemic regions. This vaccine contains a recombinant B subunit of the cholera toxin that is antigenically similar to the heat labile toxin of ETEC...
2013: Cochrane Database of Systematic Reviews
Susannah Leach, Anna Lundgren, Ann-Mari Svennerholm
We show that the kinetics of circulating IgA as well as IgG antibody-secreting cell (ASC) responses differs considerably after primary and booster vaccination with the oral cholera vaccine Dukoral(®), as determined by the antibody in lymphocyte supernatant (ALS) as well as ELISPOT methods. Thus, whereas the antitoxin ASC responses did not peak until 7-9 days after primary vaccination, peak responses to a second dose given after two weeks, or a single booster dose given 6 months to 14 years later, were recorded already after 4-5 days and then rapidly declined...
June 26, 2013: Vaccine
Dmitry Kurouski, Karunakar Kar, Ronald Wetzel, Rina K Dukor, Igor K Lednev, Laurence A Nafie
Polyglutamine (PolyQ) aggregates are a hallmark of several severe neurodegenerative diseases, expanded CAG-repeat diseases in which inheritance of an expanded polyQ sequence above a pathological threshold is associated with a high risk of disease. Application of vibrational circular dichroism (VCD) reveals that these PolyQ fibril aggregates exhibit a chiral supramolecular organization that is distinct from the supramolecular organization of previously observed amyloid fibrils. PolyQ fibrils grown from monomers with Q repeats 35 and above (Q≥35) exhibit approximately 10-fold enhancement of the same VCD spectrum compared to the already enhanced VCD of fibrils formed from Q repeats 30 and below (Q≤30)...
June 5, 2013: FEBS Letters
G Gabutti, M Aquilina, M Cova, S Giuffrida, A Lizioli, D Protano, F Scrivano, A Tomasi, A Cucchi, A Cavallaro
INTRODUCTION: Estimate the efficacy of oral anticholeric vaccine Dukoral in subjects travelling to high-risk areas for traveler's diarrhoea and cholera. METHODS: The study involved subjects of both genders who planned to travel to high-risk areas for traveler's diarrhoea and cholera. Immunization with oral anticholeric vaccine Dukoral was offered to each one of them. Upon returning, all the participants in the study were asked to complete a self-administered questionnaire consisting of 40 close-ended questions mainly concerning: personal and health data, characteristics (length, destination, reason) of the travel, onset of gastrointestinal symptoms, data relating to the assumption of anticholeric vaccine and possible adverse reactions...
December 2012: Journal of Preventive Medicine and Hygiene
Ali Azizi, Haitham Ghunaim, Danylo Sirskyj, Firouzeh Fallahi, Hoang Thanh Le, Ashok Kumar
Oral vaccines have several attractive features; however, due to several challenges, to date, only a limited number of oral vaccines are licensed. Over the past two decades, several oral vehicle delivery systems have been developed to address these challenges and deliver antigens to the target cells in the mucosal immune system. While the size of vehicle delivery systems, the quantity of components in the vehicle formulation, the dose of administration, and even the type of animals species, are important aspects in development of a suitable oral vaccine, our results showed that entrapment of inactivated Vibrio cholera, a component in the structure of Dukoral vaccine into oral vehicle delivery systems, is able to induce a more rigorous humoral immune response in the systemic compartment...
July 2013: Human Vaccines & Immunotherapeutics
Alessandra Giugliarelli, Paola Sassi, Marco Paolantoni, Assunta Morresi, Rina Dukor, Laurence Nafie
Vibrational spectroscopy has been applied to the study of conformational variation of lysozyme during thermal denaturation. An infrared and vibrational circular dichroism (VCD) analysis of lysozyme in D2O, D2O/EtOD, and D2O/DMSO at different solvent compositions and pH's was accomplished. Complete deuteration effects on amidic groups were revealed through the analysis of the amide I band of lysozyme dissolved in deuterated water. The comparison of IR absorption and VCD spectra of lysozyme in D2O revealed the higher sensitivity of the VCD technique to the presence of partially or fully deuterated secondary structure of lysozyme...
March 7, 2013: Journal of Physical Chemistry. B
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