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Peptide Vaccine
Published in Mesut Karahan, Synthetic Peptide Vaccine Models, 2021
Joel Lim Whye Ern, Tan Shen Leng, Tee Yi Na, Palaniarajan Vijayaraj Kumar
The safety and efficacy of vaccines against infectious diseases largely depends on the quality of the vaccines. Unlike chemical drugs, vaccines are required to be stored and transported at recommended temperatures from the time of manufacture to the point of administration in order to maintain product quality. Improper vaccine storage and handling will lead to decline in a vaccine’s effectiveness and the ineffectiveness of a vaccine only becomes evident when the immunized personnel acquire the disease that the vaccine was designed to prevent. Thus, vaccine formulation plays a critical role in improving vaccine stability and provides an optimal efficacy and safety as there is a need to develop vaccines which are stable in a range of conditions. In a recent study, alumina-encapsulated vaccine formulation showed improved thermostability and immunogenicity in a live-attenuated strain of human enterovirus 71 (Bay et al. 1997). Oil-in-water emulsion MF59 adjuvant required a lower dose of antigen and is more potent for both antibody and T cell responses (O’Hagan 2007). VLP technology is one of the main focuses on developing new vaccines which offer potentially safer and cheaper vaccine candidates. Engineered VLPs are able to improve the stability of a vaccine and allow a longer shelf-life, enhance thermostability, and reduce cost in maintaining cold-chain during storage and transportation (Frietze, Peabody, and Chackerian 2016).
Evolution
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Furthermore, Domingo-Calap et al. (2010) examined the correlation between mutational robustness and thermostability in the experimental Qβ populations. Thus, the thermostable viruses evolved after only six serial passages in the presence of heat shocks, and genome sequencing suggested that thermostability can be conferred by several alternative mutations. To test whether thermostable viruses have increased mutational robustness, additional passages in the presence of nitrous acid were performed. Whereas in control lines this treatment produced the expected reduction in growth rate caused by the accumulation of deleterious mutations, the thermostable viruses showed no such reduction, indicating that they were more resistant to mutagenesis. This suggested that the selection for thermostability could lead to the emergence of mutational robustness driven by plastogenetic congruence (Domingo-Calap et al. 2010).
Molecular Analysis of Plant DNA Genomes: Conserved and Diverged DNA Sequences
Published in S. K. Dutta, DNA Systematics, 2019
Additional data were obtained in assays with Sc DNA of S. mucronatum (2C) (Table 2); the thermostability of DNA hybrids obtained in the experiment with S. mucronatum (2C) and S. mucronatum (6C) (ΔTm = 4.0°C) was close to that found in interspecies hybrids. The lowest thermostability (ΔTm = 7 to 19°C) was registered in intergeneric hybridization experiments.
Toward generalizable prediction of antibody thermostability using machine learning on sequence and structure features
Published in mAbs, 2023
Ameya Harmalkar, Roshan Rao, Yuxuan Richard Xie, Jonas Honer, Wibke Deisting, Jonas Anlahr, Anja Hoenig, Julia Czwikla, Eva Sienz-Widmann, Doris Rau, Austin J. Rice, Timothy P. Riley, Danqing Li, Hannah B. Catterall, Christine E. Tinberg, Jeffrey J. Gray, Kathy Y. Wei
Thermostability is an important determinant of developability. To address the limitations in developing thermostable biological candidates, antibody engineering efforts are directed toward identifying and screening for sequences that can improve thermostability. In this work, we have tested two approaches for prediction of thermostable scFv sequences from features learned with a sequential and thermodynamic context. As the corpus of sequence databases is vast (billions of sequences from diverse protein families), we equipped the unsupervised learned representations via pre-trained language models to classify sequences into temperature-specific bins quantifying their thermostability. Unlike conventional machine-learning approaches that use sequence or structural-coordinate features, we incorporated enriched information with thermodynamic features. Further, we tested the performance of using energetic features on small, supervised CNN models for the classification tasks. Finally, we demonstrated the applicability of our work for antibody engineering efforts by identifying experimentally validated melting temperature (Tm) enhancing mutations on an anti-VEGF antibody. While the primary objective of this work was to study proof-of-principle for scFv thermostability classification with machine-learning models, the secondary objective was to identify ‘generalizable’ feature representations that can aid in creating a pipeline for rapid, computational screening and validation of scFv and antibody sequences based on their thermal characteristics.
AlbuCORE: an albumin-based molecular scaffold for multivalent biologics design
Published in mAbs, 2020
Mario Sanches, Igor D’Angelo, Maria Jaramillo, Jason Baardsnes, John Zwaagstra, Joe Schrag, Ian Schoenhofen, Mauro Acchione, Sam Lawn, Grant Wickman, Nina Weisser, David K. Y. Poon, Gordon Ng, Surjit Dixit
To validate the structural integrity of the AlbuCORE heterodimers, we compared the Far UV circular dichroism (CD) spectra of HSA with each of the AlbuCORE scaffolds, in particular the wavelength minima for the typical alpha-helical bands (Figure 3a, inset). There is a high degree of overlap among the HSA and the AlbuCORE spectra, with the exception of AlbuCORE_7, which shows a lower ellipticity signal at the expected alpha-helix range. Finally, we also compared the thermostability of each AlbuCORE construct with that of HSA using differential scanning calorimetry (DSC). Under these assay conditions, the HSA DSC thermograms can be deconvoluted into three transitions. The majority of the Tm1 transitions for the AlbuCORE constructs are within 5°C of HSA Tm1 (lowest transition temperature), as shown in Figure 3b. Exceptions are the AlbuCORE_1 and 2 constructs, with Tm1 reduced by about 10°C. We initially observed a high degree of variability in the transition melting temperatures among independent replicates for the recombinant HSA and AlbuCORE constructs. Reproducible thermal stability results were obtained by adding excess fatty acid (20 molar equivalents octanoic acid) and heat treating (simulating pasteurization) the samples prior to DSC measurements.52,53 DSC thermograms of the untreated samples can be seen in Supplementary Figure 2.
Fatty acids and survival of bacteria in Hammam Pharaon springs, Egypt
Published in Egyptian Journal of Basic and Applied Sciences, 2018
Yehia A. Osman, Mahmud Mokhtar Gbr, Ahmed Abdelrazak, Amr M. Mowafy
Extremophiles are members of the extreme environment-tolerant organisms, which belong to Archaea, eubacteria, and eukaryote. These group of organisms can live, survive and flourish at temperatures above 50 °C and may reach 80 °C and up [1]. The normal temperature sensitive macromolecules (enzymes, proteins, lipids and nucleic acids) have demonstrated tolerance/resistance to this denaturing high temperatures. This adaptability of the thermophiles and hyperthermophiles cellular components is simply described as thermostability. These thermophiles and hyperthermophiles bacteria have been isolated from different habitats including hydrothermal vents and deep ocean-basin cores. From amongst them Gram positive/negative, spore or non-spore forming bacteria were isolated which exhibited aerobic or anaerobic metabolism [2] (See Table 1).