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M van Splunter, E van Hoffen, E G Floris-Vollenbroek, H Timmerman, E Lucas-van de Bos, B Meijer, L H Ulfman, B Witteman, J M Wells, S Brugman, H F J Savelkoul, R J J van Neerven
Oral cholera vaccination is used to induce immune responses in the intestines to protect against cholera infection. However, oral vaccination may also affect immune responses in other mucosal tissues. To study this, tissue-specific homing potential and kinetics of B-cell responses were characterized after oral cholera vaccination. Healthy adult volunteers received two doses of Dukoral® and blood, saliva, nasal wash, and fecal samples were collected over time to detect vaccine-specific antibodies. Additionally, homing potential of lymphocytes to small intestine, colon, airways, skin, and periphery was measured by expression of Integrin β1 and β7, CCR9, CCR10, CCR7, and CLA...
February 21, 2018: Mucosal Immunology
Joshua M Royal, Nobuyuki Matoba
Cholera toxin B subunit (CTB) is a mucosal immunomodulatory protein that induces robust mucosal and systemic antibody responses. This well-known biological activity has been exploited in cholera prevention (as a component of Dukoral® vaccine) and vaccine development for decades. On the other hand, several studies have investigated CTB's immunotherapeutic potential in the treatment of inflammatory diseases such as Crohn's disease and asthma. Furthermore, we recently found that a variant of CTB could induce colon epithelial wound healing in mouse colitis models...
November 23, 2017: Toxins
Markéta Pazderková, Tomáš Pazderka, Maruda Shanmugasundaram, Rina K Dukor, Igor K Lednev, Laurence A Nafie
Supramolecular chirality of amyloid fibrils, protein aggregates related to many neurodegenerative diseases, is a remarkable property associated with fibril structure and polymorphism. Since its discovery almost 10 years ago there is still little understanding of this phenomenon, including the cause of the highly enhanced vibrational circular dichroism (VCD) intensity arising from fibril supramolecular chirality. In this study, VCD spectra, enhanced by filament supramolecular chirality, are presented for lysozyme and insulin fibrils above and below pH 2 and after deuterium exchange, above and below pD 2...
September 2017: Chirality
Xuefang Lu, Honggang Li, Jordan W Nafie, Tomáš Pazderka, Markéta Pazderková, Rina K Dukor, Laurence A Nafie
We report the first vibrational circular dichroism (VCD) measurement of spatial heterogeneity in a sample using infrared (IR) microsampling. Vibrational circular dichroism spectra are typically measured using a standard IR cell with an IR beam diameter of 10 mm or greater making it impossible to investigate the spatial heterogeneity of a solid film sample. We have constructed a VCD sampling assembly with either 3 mm or 1 mm spatial resolution. An XY-translation stage was used to measure spectra at different spatial locations producing IR and VCD maps of the sample...
June 2017: Applied Spectroscopy
Anja Rüther, Aurelien Forget, Anjan Roy, Carolina Carballo, Florian Mießmer, Rina K Dukor, Laurence A Nafie, Christian Johannessen, V Prasad Shastri, Steffen Lüdeke
The mechanical properties of agarose-derived hydrogels depend on the scaffolding of the polysaccharide network. To identify and quantify such higher order structure, we applied Raman optical activity (ROA)-a spectroscopic technique that is highly sensitive toward carbohydrates-on native agarose and chemically modified agarose in the gel phase for the first time. By spectral global fitting, we isolated features that change as a function of backbone carboxylation (28, 40, 50, 60, 80, and 93 %) from other features that remain unchanged...
April 10, 2017: Angewandte Chemie
Marjahan Akhtar, Firdausi Qadri, Taufiqur R Bhuiyan, Sarmin Akter, Tanzeem A Rafique, Arifuzzaman Khan, Laila N Islam, Amit Saha, Ann-Mari Svennerholm, Anna Lundgren
Immune responses to oral enteric vaccines in children and infants may be influenced by factors such as age, previous priming with related microorganisms and breast feeding. In this study, we aimed to determine optimal time points to assess immune responses to oral enteric vaccines in different clinical specimens. This was done by investigating antibody secreting cell (ASC) and fecal antibody responses on different days after vaccination using the licensed oral cholera vaccine Dukoral, containing cholera toxin B-subunit (rCTB) and inactivated Vibrio cholerae bacteria, as a model vaccine...
January 5, 2017: Vaccine
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...
July 2, 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
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