An overview of progress from empirical to rational design in modern vaccine development, with an emphasis on computational tools and immunoinformatics approaches

2021 ◽  
pp. 105057
Author(s):  
Safoura Soleymani ◽  
Amin Tavassoli ◽  
Mohammad Reza Housaindokht
Keyword(s):  
Rational Design ◽  
Vaccine Development ◽  
Computational Tools

Molecular Design of Peptide-Fc Fusion Drugs

2019 ◽  
Vol 20 (3) ◽  
pp. 203-208 ◽  
Author(s):  
Lin Ning ◽  
Bifang He ◽  
Peng Zhou ◽  
Ratmir Derda ◽  
Jian Huang
Keyword(s):  
Rational Design ◽  
Molecular Design ◽  
Computational Design ◽  
Fusion Technology ◽  
Computational Tools ◽  
Open Questions ◽  
Biological Therapeutics ◽  
Key Steps ◽  
Computational Resources ◽  
Tools And Methods

Background:Peptide-Fc fusion drugs, also known as peptibodies, are a category of biological therapeutics in which the Fc region of an antibody is genetically fused to a peptide of interest. However, to develop such kind of drugs is laborious and expensive. Rational design is urgently needed.Methods:We summarized the key steps in peptide-Fc fusion technology and stressed the main computational resources, tools, and methods that had been used in the rational design of peptide-Fc fusion drugs. We also raised open questions about the computer-aided molecular design of peptide-Fc.Results:The design of peptibody consists of four steps. First, identify peptide leads from native ligands, biopanning, and computational design or prediction. Second, select the proper Fc region from different classes or subclasses of immunoglobulin. Third, fuse the peptide leads and Fc together properly. At last, evaluate the immunogenicity of the constructs. At each step, there are quite a few useful resources and computational tools.Conclusion:Reviewing the molecular design of peptibody will certainly help make the transition from peptide leads to drugs on the market quicker and cheaper.

scholarly journals A cookbook for DNase Hi-C

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Maria Gridina ◽  
Evgeniy Mozheiko ◽  
Emil Valeev ◽  
Ludmila P. Nazarenko ◽  
Maria E. Lopatkina ◽  
...  
Keyword(s):  
Rational Design ◽  
Restriction Enzymes ◽  
Nucleotide Exchange ◽  
Computational Tools ◽  
3 Dimensional ◽  
Cultured Human Cells ◽  
Dna Ends ◽  
By Products ◽  
Robust Protocol

Abstract Background The Hi-C technique is widely employed to study the 3-dimensional chromatin architecture and to assemble genomes. The conventional in situ Hi-C protocol employs restriction enzymes to digest chromatin, which results in nonuniform genomic coverage. Using sequence-agnostic restriction enzymes, such as DNAse I, could help to overcome this limitation. Results In this study, we compare different DNAse Hi-C protocols and identify the critical steps that significantly affect the efficiency of the protocol. In particular, we show that the SDS quenching strategy strongly affects subsequent chromatin digestion. The presence of biotinylated oligonucleotide adapters may lead to ligase reaction by-products, which can be avoided by rational design of the adapter sequences. Moreover, the use of nucleotide-exchange enzymes for biotin fill-in enables simultaneous labelling and repair of DNA ends, similar to the conventional Hi-C protocol. These improvements simplify the protocol, making it less expensive and time-consuming. Conclusions We propose a new robust protocol for the preparation of DNAse Hi-C libraries from cultured human cells and blood samples supplemented with experimental controls and computational tools for the evaluation of library quality.

scholarly journals Induction of Protective Antiplague Immune Responses by Self-Adjuvanting Bionanoparticles Derived from Engineered Yersinia pestis

2020 ◽  
Vol 88 (5) ◽  
Author(s):  
Xiuran Wang ◽  
Amit K. Singh ◽  
Xiangmin Zhang ◽  
Wei Sun
Keyword(s):  
Immune Responses ◽  
Yersinia Pestis ◽  
Rational Design ◽  
Lipid A ◽  
Vaccine Development ◽  
Lethal Dose ◽  
Outer Membrane Vesicles ◽  
Vector System ◽  
Content Type ◽  
Monophosphoryl Lipid A

ABSTRACT A Yersinia pestis mutant synthesizing an adjuvant form of lipid A (monophosphoryl lipid A, MPLA) displayed increased biogenesis of bacterial outer membrane vesicles (OMVs). To enhance the immunogenicity of the OMVs, we constructed an Asd-based balanced-lethal host-vector system that oversynthesized the LcrV antigen of Y. pestis, raised the amounts of LcrV enclosed in OMVs by the type II secretion system, and eliminated harmful factors like plasminogen activator (Pla) and murine toxin from the OMVs. Vaccination with OMVs containing MPLA and increased amounts of LcrV with diminished toxicity afforded complete protection in mice against subcutaneous challenge with 8 × 105 CFU (80,000 50% lethal dose [LD50]) and intranasal challenge with 5 × 103 CFU (50 LD50) of virulent Y. pestis. This protection was significantly superior to that resulting from vaccination with LcrV/alhydrogel or rF1-V/alhydrogel. At week 4 postimmunization, the OMV-immunized mice showed more robust titers of antibodies against LcrV, Y. pestis whole-cell lysate (YPL), and F1 antigen and more balanced IgG1:IgG2a/IgG2b-derived Th1 and Th2 responses than LcrV-immunized mice. Moreover, potent adaptive and innate immune responses were stimulated in the OMV-immunized mice. Our findings demonstrate that self-adjuvanting Y. pestis OMVs provide a novel plague vaccine candidate and that the rational design of OMVs could serve as a robust approach for vaccine development.

Aggrescan3D standalone package for structure-based prediction of protein aggregation properties

2019 ◽  
Vol 35 (19) ◽  
pp. 3834-3835 ◽  
Author(s):  
Aleksander Kuriata ◽  
Valentin Iglesias ◽  
Mateusz Kurcinski ◽  
Salvador Ventura ◽  
Sebastian Kmiecik
Keyword(s):  
Protein Aggregation ◽  
Rational Design ◽  
Protein Solubility ◽  
Automated Analysis ◽  
Computational Framework ◽  
Computational Tools ◽  
Non Profit ◽  
Recent Experimental Study ◽  
The Impact ◽  
Python Package

Abstract Summary Aggrescan3D (A3D) standalone is a multiplatform Python package for structure-based prediction of protein aggregation properties and rational design of protein solubility. A3D allows the re-design of protein solubility by combining structural aggregation propensity and stability predictions, as demonstrated by a recent experimental study. It also enables predicting the impact of protein conformational fluctuations on the aggregation properties. The standalone A3D version is an upgrade of the original web server implementation—it introduces a number of customizable options, automated analysis of multiple mutations and offers a flexible computational framework for merging it with other computational tools. Availability and implementation A3D standalone is distributed under the MIT license, which is free for academic and non-profit users. It is implemented in Python. The A3D standalone source code, wiki with documentation and examples of use, and installation instructions for Linux, macOS and Windows are available in the A3D standalone repository at https://bitbucket.org/lcbio/aggrescan3d.

scholarly journals Next-Generation Technologies and Systems Biology for the Design of Novel Vaccines Against Apicomplexan Parasites

2022 ◽  
Vol 8 ◽  
Author(s):  
Mariela Luján Tomazic ◽  
Virginia Marugan-Hernandez ◽  
Anabel Elisa Rodriguez
Keyword(s):  
Systems Biology ◽  
Rational Design ◽  
Vaccine Development ◽  
Genetic Manipulation ◽  
Holistic View ◽  
Apicomplexan Parasites ◽  
Sequencing Technologies ◽  
Causative Agents ◽  
Parasite Biology ◽  
Potential Vaccine

Parasites of the phylum Apicomplexa are the causative agents of important diseases such as malaria, toxoplasmosis or cryptosporidiosis in humans, and babesiosis and coccidiosis in animals. Whereas the first human recombinant vaccine against malaria has been approved and recently recommended for wide administration by the WHO, most other zoonotic parasitic diseases lack of appropriate immunoprophylaxis. Sequencing technologies, bioinformatics, and statistics, have opened the “omics” era into apicomplexan parasites, which has led to the development of systems biology, a recent field that can significantly contribute to more rational design for new vaccines. The discovery of novel antigens by classical approaches is slow and limited to very few antigens identified and analyzed by each study. High throughput approaches based on the expansion of the “omics”, mainly genomics and transcriptomics have facilitated the functional annotation of the genome for many of these parasites, improving significantly the understanding of the parasite biology, interactions with the host, as well as virulence and host immune response. Developments in genetic manipulation in apicomplexan parasites have also contributed to the discovery of new potential vaccine targets. The present minireview does a comprehensive summary of advances in “omics”, CRISPR/Cas9 technologies, and in systems biology approaches applied to apicomplexan parasites of economic and zoonotic importance, highlighting their potential of the holistic view in vaccine development.

scholarly journals Toward the Rational Design of a Malaria Vaccine Construct Using the MSP3 Family as an Example: Contribution of Antigenicity Studies in Humans

2009 ◽  
Vol 78 (1) ◽  
pp. 486-494 ◽  
Author(s):  
Corine G. Demanga ◽  
Lena-Juliette Daher ◽  
Eric Prieur ◽  
Catherine Blanc ◽  
Jean-Louis Pérignon ◽  
...  
Keyword(s):  
Rational Design ◽  
Vaccine Development ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Native Proteins ◽  
Malaria Vaccines ◽  
Igg3 Subclass ◽  
And Function ◽  
The Village ◽  
Similar Organization

ABSTRACT Plasmodium falciparum merozoite surface protein (MSP3) is a main target of protective immunity against malaria that is currently undergoing vaccine development. It was shown recently to belong, together with MSP6, to a new multigene family whose C-terminal regions have a similar organization, contain both homologous and divergent regions, and are highly conserved across isolates. In an attempt to rationally design novel vaccine constructs, we extended the analysis of antigenicity and function of region-specific antibodies, previously performed with MSP3 and MSP6, to the remaining four proteins of the MSP3 family using four recombinant proteins and 24 synthetic peptides. Antibodies to each MSP3 family antigen were found to be highly prevalent among malaria-exposed individuals from the village of Dielmo (Senegal). Each of the 24 peptides was antigenic, defining at least one epitope mimicking that of the native proteins, with a distinct IgG isotype pattern for each, although with an overall predominance of the IgG3 subclass. Human antibodies affinity purified upon each of the 24 peptides exerted an antiparasite antibody-dependent cellular inhibition effect, which in most cases was as strong as that of IgG from protected African adults. The two regions with high homology were found to generate a broad network of cross-reactive antibodies with various avidities. A first multigenic construct was designed using these findings and those from related immunogenicity studies in mice and demonstrated valuable immunological properties. These results indicate that numerous regions from the MSP3 family play a role in protection and provide a rationale for the tailoring of new MSP3-derived malaria vaccines.

An overview of aptamer: the prominent applications and different computational tools for its design

2020 ◽  
Vol 21 ◽  
Author(s):  
Mehrdad Ameri ◽  
Sedigheh Eskandari ◽  
Navid Nezafat
Keyword(s):  
Vaccine Development ◽  
3D Structure ◽  
Therapeutic Vaccine ◽  
Cost Effective ◽  
Computational Tools ◽  
High Affinity ◽  
Aptamer Selection ◽  
Effective Role ◽  
Systematic Evolution ◽  
Selection Of

Background: Aptamers are short single-stranded oligonucleotides; due to their 3D structure, they can specifically bind to various targets. They can target several molecules ranging from metal ions, organic components to proteins, and large cells. Methods: According to the high affinity of aptamers, they can be used for diagnosis, therapeutic, vaccine development, and gene silencing applications. The conventional method for aptamer selection is known as the systematic evolution of ligands by exponential (SELEX). However, despite the efficiency of SELEX as a screening procedure, it is beneficial to develop more rational procedures for aptamer selection. Results & Discussion: Herein, in silico approaches can play an effective role given their potential in representing an efficient, cost-effective, parallelizable, and rapid strategy. In recent years, several attempts have been applied to develop algorithms and software for the rational selection of aptamers. However, there is still a need for more efforts to achieve the most efficient techniques in this area. Conclusion: In this review, we aim to overview different computational approaches that are used for aptamer selection.

Membrane Protein Structures for Rational Antimicrobial Drug Design

2014 ◽  
Vol 67 (12) ◽  
pp. 1724 ◽  
Author(s):  
Patricia M. Walden ◽  
Roisin M. McMahon ◽  
Julia K. Archbold
Keyword(s):  
Membrane Proteins ◽  
Poor Prognosis ◽  
Rational Design ◽  
Vaccine Development ◽  
Protein Structures ◽  
Resistance Mechanisms ◽  
Bacterial Membrane ◽  
Gram Negative Bacteria ◽  
Drug Resistant

Antibiotic resistance is a major global health threat. Bacteria have developed novel resistance mechanisms to many of the latest generations of antibiotics and there is an urgent need to develop new therapies to combat these infections. Infections that are caused by multi-drug resistant Gram-negative bacteria result in poor prognosis, prolonged illness, and greater costs for health care. Recent research has pointed to several key bacterial membrane proteins as potential targets for drug and vaccine development. However, determination of the structures of these membrane proteins is not a trivial task. Here we review recent breakthroughs of the structural determination of bacterial membrane proteins and their potential for the future rational design of novel antimicrobial therapies.

scholarly journals Actinoporins: From the Structure and Function to the Generation of Biotechnological and Therapeutic Tools

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 539 ◽  
Author(s):  
Santos Ramírez-Carreto ◽  
Beatriz Miranda-Zaragoza ◽  
Claudia Rodríguez-Almazán
Keyword(s):  
Rational Design ◽  
Vaccine Development ◽  
Molecular Probes ◽  
Immunomodulatory Activity ◽  
Molecular Tools ◽  
Sea Anemones ◽  
Liposomal Formulations ◽  
Conformational Plasticity ◽  
Therapeutic Tools ◽  
And Function

Actinoporins (APs) are a family of pore-forming toxins (PFTs) from sea anemones. These biomolecules exhibit the ability to exist as soluble monomers within an aqueous medium or as constitutively open oligomers in biological membranes. Through their conformational plasticity, actinoporins are considered good candidate molecules to be included for the rational design of molecular tools, such as immunotoxins directed against tumor cells and stochastic biosensors based on nanopores to analyze unique DNA or protein molecules. Additionally, the ability of these proteins to bind to sphingomyelin (SM) facilitates their use for the design of molecular probes to identify SM in the cells. The immunomodulatory activity of actinoporins in liposomal formulations for vaccine development has also been evaluated. In this review, we describe the potential of actinoporins for use in the development of molecular tools that could be used for possible medical and biotechnological applications.

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