'Coxiella Burnetii' Vaccine Development: Lipopolysaccharide Structural Analysis

1991 ◽  
Author(s):  
Vernon N. Reinhold
Keyword(s):  
Structural Analysis ◽  
Coxiella Burnetii ◽  
Vaccine Development

scholarly journals SARS-CoV-2 Mutations in Brazil: From Genomics to Clinical Conditions

2021 ◽  
Author(s):  
Luis Timmers ◽  
Julia Peixoto ◽  
Rodrigo Ducati ◽  
Jose Fernando Bachega ◽  
Leandro Mattos Pereira ◽  
...  
Keyword(s):  
Life Cycle ◽  
Drug Discovery ◽  
Structural Analysis ◽  
Structural Biology ◽  
Vaccine Development ◽  
Protein Structures ◽  
Host Cells ◽  
High Rate ◽  
Reference Region ◽  
Clinical Conditions

Due to the high rate of transmissibility, Brazil became the new COVID-19 outbreak epicenter, being a reference region to monitor how SARS-CoV-2 is mutating and spreading. Here, we combined genomic and structural biology analysis evaluate genomes isolated from different regions of Brazil. We showed that the most prevalent mutations were located in the S, N, ORF3a and ORF6 genes, which are involved in different stages of viral life cycle and its interaction with the host cells. Structural analysis brought to light the positions of these mutations on protein structures, helping studies of structure-based drug discovery and vaccine development.<br><div></div>

scholarly journals SARS-CoV-2 mutations in Brazil: from genomics to putative clinical conditions

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Luis Fernando Saraiva Macedo Timmers ◽  
Julia Vasconcellos Peixoto ◽  
Rodrigo Gay Ducati ◽  
José Fernando Ruggiero Bachega ◽  
Leandro de Mattos Pereira ◽  
...  
Keyword(s):  
Life Cycle ◽  
Drug Discovery ◽  
Structural Analysis ◽  
Vaccine Development ◽  
Protein Structures ◽  
Viral Life Cycle ◽  
Host Cells ◽  
High Rate ◽  
Clinical Conditions

AbstractDue to the high rate of transmissibility, Brazil became the new COVID-19 outbreak epicenter and, since then, is being monitored to understand how SARS-CoV-2 mutates and spreads. We combined genomic and structural analysis to evaluate genomes isolated from different regions of Brazil and show that the most prevalent mutations were located in the S, N, ORF3a and ORF6 genes, which are involved in different stages of viral life cycle and its interaction with the host cells. Structural analysis brought to light the positions of these mutations on protein structures, contributing towards studies of selective structure-based drug discovery and vaccine development.

scholarly journals Vaccine-induced protective immunity against coxiella burnetii

2019 ◽  
Author(s):  
◽  
Lindsey Elizabeth Ledbetter
Keyword(s):  
T Cells ◽  
Coxiella Burnetii ◽  
Protective Immunity ◽  
Vaccine Development ◽  
Q Fever ◽  
Therapeutic Vaccine ◽  
T Cell Subsets ◽  
Cell Mediated Immunity ◽  
Vaccine Protection ◽  
Vaccine Immunity

Coxiella burnetii is an obligate intracellular Gram-negative bacterial pathogen and the causative agent of human Q fever. This disease presents acutely as a flu-like illness, although it can escalate to a chronic and often fatal disease when left untreated. Considering no FDA-approved vaccine exists, the creation of a safe and effective vaccine remains an important public health goal. A formalin-inactivated C. burnetii Nine Mile strain phase I whole-cell vaccine generates protective immunity in a mouse model of experimental Q fever, although the mechanisms of protection remain unclear. Chapter 3 details my work establishing an early vaccine protection model and elucidating the cellular immune response which elicits early protection. The early time point at which PIV protects has implications for its use as a therapeutic vaccine. Furthermore, the innate-driven mechanisms by which it protects can be exploited for an improved Q fever vaccine. The importance of T cells in vaccine immunity against C. burnetii is well supported, however, multiple questions remain. It is unclear how CD4+ or CD8+ T cells contribute to vaccine protection, and the role of specific CD4+ T cell subsets is unknown. IFN-[theta] is critical for primary defense against C. burnetii, though its importance in vaccine immunity is undetermined. Chapter 4 describes my work aimed at filling these knowledge gaps. Vaccine development efforts have largely focused on the generation of antibodies as a correlate of protection. It has become clear that targeting T cells is more critical to vaccine protection and a better understanding of the mechanisms of cell-mediated immunity will inform future Q fever vaccine development.

scholarly journals Mutation Y453F in the spike protein of SARS-CoV-2 enhances interaction with the mink ACE2 receptor for host adaption

2021 ◽  
Vol 17 (11) ◽  
pp. e1010053
Author(s):  
Wenlin Ren ◽  
Jun Lan ◽  
Xiaohui Ju ◽  
Mingli Gong ◽  
Quanxin Long ◽  
...  
Keyword(s):  
Structural Analysis ◽  
The Netherlands ◽  
Genetic Variant ◽  
Vaccine Development ◽  
Binding Mode ◽  
Spike Protein ◽  
Adaptive Mutation ◽  
Steric Clash ◽  
Genetic Sequences ◽  
Initial Transmission

COVID-19 patients transmitted SARS-CoV-2 to minks in the Netherlands in April 2020. Subsequently, the mink-associated virus (miSARS-CoV-2) spilled back over into humans. Genetic sequences of the miSARS-CoV-2 identified a new genetic variant known as “Cluster 5” that contained mutations in the spike protein. However, the functional properties of these “Cluster 5” mutations have not been well established. In this study, we found that the Y453F mutation located in the RBD domain of miSARS-CoV-2 is an adaptive mutation that enhances binding to mink ACE2 and other orthologs of Mustela species without compromising, and even enhancing, its ability to utilize human ACE2 as a receptor for entry. Structural analysis suggested that despite the similarity in the overall binding mode of SARS-CoV-2 RBD to human and mink ACE2, Y34 of mink ACE2 was better suited to interact with a Phe rather than a Tyr at position 453 of the viral RBD due to less steric clash and tighter hydrophobic-driven interaction. Additionally, the Y453F spike exhibited resistance to convalescent serum, posing a risk for vaccine development. Thus, our study suggests that since the initial transmission from humans, SARS-CoV-2 evolved to adapt to the mink host, leading to widespread circulation among minks while still retaining its ability to efficiently utilize human ACE2 for entry, thus allowing for transmission of the miSARS-CoV-2 back into humans. These findings underscore the importance of active surveillance of SARS-CoV-2 evolution in Mustela species and other susceptible hosts in order to prevent future outbreaks.

scholarly journals SARS-CoV-2 Mutations in Brazil: From Genomics to Clinical Conditions

2021 ◽  
Author(s):  
Luis Timmers ◽  
Julia Peixoto ◽  
Rodrigo Ducati ◽  
Jose Fernando Bachega ◽  
Leandro Mattos Pereira ◽  
...  
Keyword(s):  
Life Cycle ◽  
Drug Discovery ◽  
Structural Analysis ◽  
Structural Biology ◽  
Vaccine Development ◽  
Protein Structures ◽  
Host Cells ◽  
High Rate ◽  
Reference Region ◽  
Clinical Conditions

Due to the high rate of transmissibility, Brazil became the new COVID-19 outbreak epicenter, being a reference region to monitor how SARS-CoV-2 is mutating and spreading. Here, we combined genomic and structural biology analysis evaluate genomes isolated from different regions of Brazil. We showed that the most prevalent mutations were located in the S, N, ORF3a and ORF6 genes, which are involved in different stages of viral life cycle and its interaction with the host cells. Structural analysis brought to light the positions of these mutations on protein structures, helping studies of structure-based drug discovery and vaccine development.<br><div></div>

scholarly journals Structural Analysis and Epitope Prediction of MHC Class-1-Chain Related Protein-A for Cancer Vaccine Development

Vaccines ◽  
2017 ◽  
Vol 6 (1) ◽  
pp. 1 ◽  
Author(s):  
Tayo Adekiya ◽  
Raphael Aruleba ◽  
Sbonelo Khanyile ◽  
Priscilla Masamba ◽  
Babatunji Oyinloye ◽  
...  
Keyword(s):  
Structural Analysis ◽  
Cancer Vaccine ◽  
Vaccine Development ◽  
Protein A ◽  
Epitope Prediction ◽  
Related Protein ◽  
Class 1

scholarly journals Coxiella burnetii immunogenic proteins as a basis for new Q fever diagnostic and vaccine development

2017 ◽  
Vol 61 (03) ◽  
pp. 377-390 ◽  
Author(s):  
C. Gerlach ◽  
Ľ. Škultéty ◽  
K. Henning ◽  
H. Neubauer ◽  
K. Mertens
Keyword(s):  
Coxiella Burnetii ◽  
Vaccine Development ◽  
Q Fever ◽  
Immunogenic Proteins

Structural analysis of the surface-layer protein of spirillum serpens by high-resolution electron microscopy

1983 ◽  
Vol 41 ◽  
pp. 738-739
Author(s):  
W. H. Wu ◽  
R. M. Glaeser
Keyword(s):  
Electron Microscopy ◽  
Surface Layer ◽  
Structural Analysis ◽  
High Resolution ◽  
Low Dose ◽  
High Resolution Electron Microscopy ◽  
Optical Diffraction ◽  
Surface Layer Protein ◽  
Morphological Unit ◽  
Resolution Electron

Spirillum serpens possesses a surface layer protein which exhibits a regular hexagonal packing of the morphological subunits. A morphological model of the structure of the protein has been proposed at a resolution of about 25 Å, in which the morphological unit might be described as having the appearance of a flared-out, hollow cylinder with six ÅspokesÅ at the flared end. In order to understand the detailed association of the macromolecules, it is necessary to do a high resolution structural analysis. Large, single layered arrays of the surface layer protein have been obtained for this purpose by means of extensive heating in high CaCl2, a procedure derived from that of Buckmire and Murray. Low dose, low temperature electron microscopy has been applied to the large arrays.As a first step, the samples were negatively stained with neutralized phosphotungstic acid, and the specimens were imaged at 40,000 magnification by use of a high resolution cold stage on a JE0L 100B. Low dose images were recorded with exposures of 7-9 electrons/Å2. The micrographs obtained (Fig. 1) were examined by use of optical diffraction (Fig. 2) to tell what areas were especially well ordered.

RNA polymerase: Preparation and structural analysis of helical polymers

1984 ◽  
Vol 42 ◽  
pp. 152-153
Author(s):  
E. Loren Buhle ◽  
Pamela Rew ◽  
Ueli Aebi
Keyword(s):  
Structural Analysis ◽  
Rna Polymerase ◽  
Molecular Level ◽  
X Ray Diffraction ◽  
Helical Polymers ◽  
X Ray ◽  
E Coli ◽  
The Past ◽  
Ordered Arrays ◽  
Low Ionic Strength

While DNA-dependent RNA polymerase represents one of the key enzymes involved in transcription and ultimately in gene expression in procaryotic and eucaryotic cells, little progress has been made towards elucidation of its 3-D structure at the molecular level over the past few years. This is mainly because to date no 3-D crystals suitable for X-ray diffraction analysis have been obtained with this rather large (MW ~500 kd) multi-subunit (α2ββ'ζ). As an alternative, we have been trying to form ordered arrays of RNA polymerase from E. coli suitable for structural analysis in the electron microscope combined with image processing. Here we report about helical polymers induced from holoenzyme (α2ββ'ζ) at low ionic strength with 5-7 mM MnCl2 (see Fig. 1a). The presence of the ζ-subunit (MW 86 kd) is required to form these polymers, since the core enzyme (α2ββ') does fail to assemble into such structures under these conditions.

Interpreting HVEM of muscle-cell impulse networks

1992 ◽  
Vol 50 (1) ◽  
pp. 126-127
Author(s):  
Paul DeCosta ◽  
Kyugon Cho ◽  
Stephen Shemlon ◽  
Heesung Jun ◽  
Stanley M. Dunn
Keyword(s):  
Structural Analysis ◽  
Muscle Cell ◽  
Electron Micrographs ◽  
Relative Size ◽  
Automatic Classification ◽  
Nerve Fibers ◽  
Analysis Algorithm ◽  
Structural Networks

Introduction: The analysis and interpretation of electron micrographs of cells and tissues, often requires the accurate extraction of structural networks, which either provide immediate 2D or 3D information, or from which the desired information can be inferred. The images of these structures contain lines and/or curves whose orientation, lengths, and intersections characterize the overall network.Some examples exist of studies that have been done in the analysis of networks of natural structures. In, Sebok and Roemer determine the complexity of nerve structures in an EM formed slide. Here the number of nodes that exist in the image describes how dense nerve fibers are in a particular region of the skin. Hildith proposes a network structural analysis algorithm for the automatic classification of chromosome spreads (type, relative size and orientation).

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