Open Forum Infect Dis
December 2024
is the leading bacterial cause of diarrhea worldwide, with increasing levels of antibiotic resistance. The greatest burden is among children aged <5 years in low- and middle-income countries, and efforts are ongoing to develop vaccines against this pathogen. One of the challenges associated with the development of a vaccine against is the need for a multivalent vaccine covering the most prevalent serotypes.
View Article and Find Full Text PDFBackground/objectives: Typhoid and paratyphoid fever together are responsible for millions of cases and thousands of deaths per year, most of which occur in children in South and Southeast Asia. While typhoid conjugate vaccines (TCVs) are licensed, no vaccines are currently available against Paratyphi A. Here we describe the design of a Paratyphi A conjugate.
View Article and Find Full Text PDFAlum is the most used vaccine adjuvant, due to its safety, low cost and adjuvanticity to various antigens. However, the mechanism of action of alum is complex and not yet fully understood, and the immune responses elicited can be weak and antigen-dependent. While several antigens rapidly desorb from alum upon exposure to serum, phosphorylated proteins remain tightly bound through a ligand-exchange reaction with surface hydroxyls on alum.
View Article and Find Full Text PDFGlycoconjugation is a well-established technology for vaccine development: linkage of the polysaccharide (PS) antigen to an appropriate carrier protein overcomes the limitations of PS T-independent antigens, making them effective in infants and providing immunological memory. Glycoconjugate vaccines have been successful in reducing the burden of different diseases globally. However, many pathogens still require a vaccine, and many of them display a variety of glycans on their surface that have been proposed as key antigens for the development of high-valency glycoconjugate vaccines.
View Article and Find Full Text PDF(Kp) is a Gram-negative bacterium, and a leading cause of neonatal sepsis in low- and middle-income countries, often associated with anti-microbial resistance. Two types of polysaccharides are expressed on the Kp cell surface and have been proposed as key antigens for vaccine design: capsular polysaccharides (known as K-antigens, K-Ags) and O-antigens (O-Ags). Historically, Kp has been classified using capsule serotyping and although 186 distinct genotypes have been predicted so far based on sequence analysis, many structures are still unknown.
View Article and Find Full Text PDFGlycoconjugate vaccines play a major role in the prevention of infectious diseases worldwide, with significant impact on global health, enabling the polysaccharides to induce immunogenicity in infants and immunological memory. Tetanus toxoid (TT), a chemically detoxified bacterial toxin, is among the few carrier proteins used in licensed glycoconjugate vaccines. The recombinant full-length 8MTT was engineered in with eight individual amino acid mutations to inactivate three toxin functions.
View Article and Find Full Text PDFShigellosis is a leading cause of diarrheal disease in low-middle-income countries (LMICs). Effective vaccines will help to reduce the disease burden, exacerbated by increasing antibiotic resistance, in the most susceptible population represented by young children. A challenge for a broadly protective vaccine against shigellosis is to cover the most epidemiologically relevant serotypes among >50 Shigella serotypes circulating worldwide.
View Article and Find Full Text PDFThe study of marine Lagrangian transport holds significant importance from a scientific perspective as well as for practical applications such as environmental-pollution responses and prevention (e.g., oil spills, dispersion/accumulation of plastic debris, etc.
View Article and Find Full Text PDFThis paper reviews the state of the art and discusses recent developments in the field of adaptive isogeometric analysis, with special focus on the mathematical theory. This includes an overview of available spline technologies for the local resolution of possible singularities as well as the state-of-the-art formulation of convergence and quasi-optimality of adaptive algorithms for both the finite element method and the boundary element method in the frame of isogeometric analysis.
View Article and Find Full Text PDFis a leading diarrheal cause of morbidity and mortality worldwide, especially in low- and middle-income countries and in children under five years of age. Increasing levels of antimicrobial resistance make vaccine development an even higher global health priority. serotype 6 is one of the targets of many multicomponent vaccines in development to ensure broad protection against .
View Article and Find Full Text PDFOuter membrane vesicles (OMV) represent a promising platform for the development of vaccines against bacterial pathogens. More recently, bacteria have been genetically modified to increase OMV yield and modulate the design of resulting particles, also named generalized modules for membrane antigens (GMMA). OMV/GMMA resemble the bacterial surface of the pathogen, where key antigens to elicit a protective immune response are and contain pathogen-associated molecular patterns (e.
View Article and Find Full Text PDFOuter Membrane Vesicles (OMV) constitute a promising platform for the development of efficient vaccines. OMV can be decorated with heterologous antigens (proteins or polysaccharides), becoming attractive novel carriers for the development of multicomponent vaccines. Chemical conjugation represents a tool for linking antigens, also from phylogenetically distant pathogens, to OMV.
View Article and Find Full Text PDFBlockchain technology plays a pivotal role in the undergoing fourth industrial revolution or Industry 4.0. It is considered a tremendous boost to company digitalization; thus, considerable investments in blockchain are being made.
View Article and Find Full Text PDFEnsuring the stability of vaccines is crucial to successfully performing global immunization programs. Outer Membrane Vesicles (OMV) are receiving great attention as vaccine platforms. OMV are complex molecules and few data have been collected so far on their stability.
View Article and Find Full Text PDFImprovements in cancer care over the years have increased the numbers of cancer survivors. Therefore, quality of life, fat mass management and physical activity are growing areas of interest in these people. After the surgical removal of a breast cancer, adjuvant therapy remains anyway a common strategy.
View Article and Find Full Text PDFConformational variability and heterogeneity are crucial determinants of the function of biological macromolecules. The possibility of accessing this information experimentally suffers from severe under-determination of the problem, since there are a few experimental observables to be accounted for by a (potentially) infinite number of available conformational states. Several computational methods have been proposed over the years in order to circumvent this theoretically insurmountable obstacle.
View Article and Find Full Text PDFA variety of bacterial infections have been tackled by glycoconjugates over the recent years, and more vaccines are either under development at preclinical level or in clinical trials. So far, licensed glycoconjugate vaccines have made use of capsular polysaccharides or derived fragments. Today, many glycoconjugates are making use of other classes of sugars, in particular, the O-antigen portion of lipopolysaccharide molecules.
View Article and Find Full Text PDFPolysaccharide-protein conjugates have been developed to overcome the T-independent response, hyporesponsiveness to repeated vaccination, and poor immunogenicity in infants of polysaccharides. To address the impact of polysaccharide length, typhoid conjugates made with short- and long-chain fractions of Vi polysaccharide with average sizes of 9.5, 22.
View Article and Find Full Text PDF