scholarly journals Development of multivalent mRNA vaccine candidates for seasonal or pandemic influenza

npj Vaccines ◽  
2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Sudha Chivukula ◽  
Timothy Plitnik ◽  
Timothy Tibbitts ◽  
Shrirang Karve ◽  
Anusha Dias ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Seasonal Influenza ◽  
Protective Efficacy ◽  
Rapid Development ◽  
Cellular Responses ◽  
Viral Disease ◽  
Full Length ◽  
Wide Range ◽  
Single Antigen ◽  
Viral Subtypes

AbstractRecent approval of mRNA vaccines for emergency use against COVID-19 is likely to promote rapid development of mRNA-based vaccines targeting a wide range of infectious diseases. Compared to conventional approaches, this vaccine modality promises comparable potency while substantially accelerating the pace of development and deployment of vaccine doses. Already demonstrated successfully for single antigen vaccines such as for COVID-19, this technology could be optimized for complex multi-antigen vaccines. Herein, utilizing multiple influenza antigens, we demonstrated the suitability of the mRNA therapeutic (MRT) platform for such applications. Seasonal influenza vaccines have three or four hemagglutinin (HA) antigens of different viral subtypes. In addition, influenza neuraminidase (NA), a tetrameric membrane protein, is identified as an antigen that has been linked to protective immunity against severe viral disease. We detail the efforts in optimizing formulations of influenza candidates that use unmodified mRNA encoding full-length HA or full-length NA encapsulated in lipid nanoparticles (LNPs). HA and NA mRNA-LNP formulations, either as monovalent or as multivalent vaccines, induced strong functional antibody and cellular responses in non-human primates and such antigen-specific antibody responses were associated with protective efficacy against viral challenge in mice.

Enzymes as a Reservoir of Host Defence Peptides

2020 ◽  
Vol 20 (14) ◽  
pp. 1310-1323
Author(s):  
Andrea Bosso ◽  
Antimo Di Maro ◽  
Valeria Cafaro ◽  
Alberto Di Donato ◽  
Eugenio Notomista ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Biological Activity ◽  
Internal Structure ◽  
Catalytic Properties ◽  
Cellular Responses ◽  
Host Defence ◽  
Present Review ◽  
Active Peptides ◽  
Wide Range

Host defence peptides (HDPs) are powerful modulators of cellular responses to various types of insults caused by pathogen agents. To date, a wide range of HDPs, from species of different kingdoms including bacteria, plant and animal with extreme diversity in structure and biological activity, have been described. Apart from a limited number of peptides ribosomally synthesized, a large number of promising and multifunctional HDPs have been identified within protein precursors, with properties not necessarily related to innate immunity, consolidating the fascinating hypothesis that proteins have a second or even multiple biological mission in the form of one or more bio-active peptides. Among these precursors, enzymes constitute certainly an interesting group, because most of them are mainly globular and characterized by a fine specific internal structure closely related to their catalytic properties and also because they are yet little considered as potential HDP releasing proteins. In this regard, the main aim of the present review is to describe a panel of HDPs, identified in all canonical classes of enzymes, and to provide a detailed description on hydrolases and their corresponding HDPs, as there seems to exist a striking link between these structurally sophisticated catalysts and their high content in cationic and amphipathic cryptic peptides.

scholarly journals Advanced Functional Materials Based on Nanocellulose for Pharmaceutical/Medical Applications

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1125
Author(s):  
Raluca Nicu ◽  
Florin Ciolacu ◽  
Diana E. Ciolacu
Keyword(s):  
Rapid Development ◽  
Cellulose Nanofibrils ◽  
Functional Materials ◽  
Medical Applications ◽  
Bacterial Nanocellulose ◽  
Green Materials ◽  
Wide Range ◽  
In Vivo Cytotoxicity

Nanocelluloses (NCs), with their remarkable characteristics, have proven to be one of the most promising “green” materials of our times and have received special attention from researchers in nanomaterials. A diversity of new functional materials with a wide range of biomedical applications has been designed based on the most desirable properties of NCs, such as biocompatibility, biodegradability, and their special physicochemical properties. In this context and under the pressure of rapid development of this field, it is imperative to synthesize the successes and the new requirements in a comprehensive review. The first part of this work provides a brief review of the characteristics of the NCs (cellulose nanocrystals—CNC, cellulose nanofibrils—CNF, and bacterial nanocellulose—BNC), as well as of the main functional materials based on NCs (hydrogels, nanogels, and nanocomposites). The second part presents an extensive review of research over the past five years on promising pharmaceutical and medical applications of nanocellulose-based materials, which have been discussed in three important areas: drug-delivery systems, materials for wound-healing applications, as well as tissue engineering. Finally, an in-depth assessment of the in vitro and in vivo cytotoxicity of NCs-based materials, as well as the challenges related to their biodegradability, is performed.

scholarly journals Single and Double Infections with Wolbachia in the Parasitic Wasp Nasonia vitripennis Effects on Compatibility

Genetics ◽  
1996 ◽  
Vol 143 (2) ◽  
pp. 961-972 ◽  
Author(s):  
Marie-Jeanne Perrot-Minnot ◽  
Li Rong Guo ◽  
John H Werren
Keyword(s):  
Genomic Dna ◽  
Rapid Development ◽  
Parasitic Wasp ◽  
Pcr Amplification ◽  
Bacterial Strains ◽  
Nasonia Vitripennis ◽  
Larval Diapause ◽  
Wide Range ◽  
Reproductive Incompatibility ◽  
Infected Line

Abstract Wolbachia are cytoplasmically inherited bacteria responsible for reproductive incompatibility in a wide range of insects. There has been little exploration, however, of within species Wolbachia polymorphisms and their effects on compatibility. Here we show that some strains of the parasitic wasp Nasonia vitripennis are infected with two distinct bacterial strains (A and B) whereas others are singly infected (A or B). Double and single infections are confirmed by both PCR amplification and Southern analysis of genomic DNA. Furthermore, it is shown that prolonged larval diapause (the overwintering stage of the wasp) of a double-infected strain can lead to stochastic loss of one or both bacterial strains. After diapause of a double-infected line, sublines were produced with AB, A only, B only or no Wolbachia. A and B sublines are bidirectionally incompatible, whereas males from AB lines are unidirectionally incompatible with females of A and B sublines. Results therefore show rapid development of bidirectional incompatibility within a species due to segregation of associated symbiotic bacteria.

scholarly journals Vaccination with DNA Encoding the Immunodominant LACK Parasite Antigen Confers Protective Immunity to Mice Infected with Leishmania major

1997 ◽  
Vol 186 (7) ◽  
pp. 1137-1147 ◽  
Author(s):  
Sanjay Gurunathan ◽  
David L. Sacks ◽  
Daniel R. Brown ◽  
Steven L. Reiner ◽  
Hughes Charest ◽  
...  
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Protective Immunity ◽  
Leishmania Major ◽  
Protective Efficacy ◽  
Dna Vaccination ◽  
Attractive Alternative ◽  
Dna Immunization ◽  
Dna Encoding ◽  
Ifn Γ

To determine whether DNA immunization could elicit protective immunity to Leishmania major in susceptible BALB/c mice, cDNA for the cloned Leishmania antigen LACK was inserted into a euykaryotic expression vector downstream to the cytomegalovirus promoter. Susceptible BALB/c mice were then vaccinated subcutaneously with LACK DNA and challenged with L. major promastigotes. We compared the protective efficacy of LACK DNA vaccination with that of recombinant LACK protein in the presence or absence of recombinant interleukin (rIL)-12 protein. Protection induced by LACK DNA was similar to that achieved by LACK protein and rIL-12, but superior to LACK protein without rIL-12. The immunity conferred by LACK DNA was durable insofar as mice challenged 5 wk after vaccination were still protected, and the infection was controlled for at least 20 wk after challenge. In addition, the ability of mice to control infection at sites distant to the site of vaccination suggests that systemic protection was achieved by LACK DNA vaccination. The control of disease progression and parasitic burden in mice vaccinated with LACK DNA was associated with enhancement of antigen-specific interferon-γ (IFN-γ) production. Moreover, both the enhancement of IFN-γ production and the protective immune response induced by LACK DNA vaccination was IL-12 dependent. Unexpectedly, depletion of CD8+ T cells at the time of vaccination or infection also abolished the protective response induced by LACK DNA vaccination, suggesting a role for CD8+ T cells in DNA vaccine induced protection to L. major. Thus, DNA immunization may offer an attractive alternative vaccination strategy against intracellular pathogens, as compared with conventional vaccination with antigens combined with adjuvants.

scholarly journals Vaccination with Outer Membrane Complexes Elicits Rapid Protective Immunity to Multidrug-ResistantAcinetobacter baumannii

2010 ◽  
Vol 79 (1) ◽  
pp. 518-526 ◽  
Author(s):  
Michael J. McConnell ◽  
Juan Domínguez-Herrera ◽  
Younes Smani ◽  
Rafael López-Rojas ◽  
Fernando Docobo-Pérez ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Protective Immunity ◽  
Cellular Responses ◽  
Antibiotic Resistant ◽  
Membrane Complex ◽  
Sepsis Model ◽  
Cytokine Levels ◽  
Prophylactic Vaccination ◽  
Resistant Strains ◽  
Established Infection

ABSTRACTAcinetobacter baumanniicauses pneumonias, bacteremias, and skin and soft tissue infections, primarily in the hospitalized setting. The incidence of infections caused byA. baumanniihas increased dramatically over the last 30 years, while at the same time the treatment of these infections has been complicated by the emergence of antibiotic-resistant strains. Despite these trends, no vaccines or antibody-based therapies have been developed for the prevention ofA. baumanniiinfection. In this study, an outer membrane complex vaccine consisting of multiple surface antigens from the bacterial membrane ofA. baumanniiwas developed and tested in a murine sepsis model. Immunization elicited humoral and cellular responses that were able to reduce postinfection bacterial loads, reduce postinfection proinflammatory cytokine levels in serum, and protect mice from infection with human clinical isolates ofA. baumannii. A single administration of the vaccine was able to elicit protective immunity in as few as 6 days postimmunization. In addition, vaccine antiserum was used successfully to therapeutically rescue naïve mice with established infection. These results indicate that prophylactic vaccination and antibody-based therapies based on an outer membrane complex vaccine may be viable approaches to preventing the morbidity and mortality caused by this pathogen.

ORGANIZATION OF ROAD TRAFFIC TAKING INTO ACCOUNT ELECTRIC ROUTE PASSENGER TRANSPORT

2021 ◽  
Vol 2 (65) ◽  
pp. 66-77
Author(s):  
Denis V. Kapsky ◽  
◽  
Sergey S. Semchenkov ◽  
Evgeny N. Kot ◽  
◽  
...  
Keyword(s):  
Traffic Management ◽  
Road Traffic ◽  
Rapid Development ◽  
Living Environment ◽  
Transport Sector ◽  
Passenger Transport ◽  
Wide Range ◽  
Practical Development ◽  
The Republic ◽  
Conducting Research

The rapid development of the transport sector leads not only to positive changes in the life of cities and towns, to an increase in convenience and comfort for residents, but also worsens the ecology and their living environment. The “profitable-safe” dilemma can be solved by the approach of environmentally oriented selection of the type of route passenger transport and decisionmaking in favor of electric route passenger transport. The article discusses the types of such transport on the example of the experience of their use in the Republic of Belarus. The classification and systematization developed by the authors are presented with subsequent recommendations for its application. On the basis of the results of the authors’ research, the issues of interaction of rail and non-rail route vehicles with an electric drive with the organization of road traffic are separately considered. The presented materials can be useful to a wide range of readers, as well as to specialists conducting research and practical development in the field of electrically powered route vehicles and traffic management.

scholarly journals Kinome Expansion in theFusarium oxysporumSpecies Complex Driven by Accessory Chromosomes

mSphere ◽  
2018 ◽  
Vol 3 (3) ◽  
Author(s):  
Gregory A. DeIulio ◽  
Li Guo ◽  
Yong Zhang ◽  
Jonathan M. Goldberg ◽  
H. Corby Kistler ◽  
...  
Keyword(s):  
Fusarium Oxysporum ◽  
Species Complex ◽  
Severe Disease ◽  
Cellular Responses ◽  
Human Pathogens ◽  
Content Type ◽  
Evolutionary Forces ◽  
Environmental Signal ◽  
Wide Range ◽  
Opportunistic Fungal Pathogen

ABSTRACTTheFusarium oxysporumspecies complex (FOSC) is a group of soilborne pathogens causing severe disease in more than 100 plant hosts, while individual strains exhibit strong host specificity. Both chromosome transfer and comparative genomics experiments have demonstrated that lineage-specific (LS) chromosomes contribute to the host-specific pathogenicity. However, little is known about the functional importance of genes encoded in these LS chromosomes. Focusing on signaling transduction, this study compared the kinomes of 12F. oxysporumisolates, including both plant and human pathogens and 1 nonpathogenic biocontrol strain, with 7 additional publicly available ascomycete genomes. Overall,F. oxysporumkinomes are the largest, facilitated in part by the acquisitions of the LS chromosomes. The comparative study identified 99 kinases that are present in almost all examined fungal genomes, forming the core signaling network of ascomycete fungi. Compared to the conserved ascomycete kinome, the expansion of theF. oxysporumkinome occurs in several kinase families such as histidine kinases that are involved in environmental signal sensing and target of rapamycin (TOR) kinase that mediates cellular responses. Comparative kinome analysis suggests a convergent evolution that shapes individualF. oxysporumisolates with an enhanced and unique capacity for environmental perception and associated downstream responses.IMPORTANCEIsolates ofFusarium oxysporumare adapted to survive a wide range of host and nonhost conditions. In addition,F. oxysporumwas recently recognized as the top emerging opportunistic fungal pathogen infecting immunocompromised humans. The sensory and response networks of these fungi undoubtedly play a fundamental role in establishing the adaptability of this group. We have examined the kinomes of 12F. oxysporumisolates and highlighted kinase families that distinguishF. oxysporumfrom other fungi, as well as different isolates from one another. The amplification of kinases involved in environmental signal relay and regulating downstream cellular responses clearly setsFusariumapart from otherAscomycetes. Although the functions of many of these kinases are still unclear, their specific proliferation highlights them as a result of the evolutionary forces that have shaped this species complex and clearly marks them as targets for exploitation in order to combat disease.

Genetically-determined influences on the ability of poor responder mice to respond to immunization against Trichuris muris

Parasitology ◽  
1990 ◽  
Vol 100 (3) ◽  
pp. 479-489 ◽  
Author(s):  
K. J. Else ◽  
D. Wakelin
Keyword(s):  
Molecular Weight ◽  
High Molecular Weight ◽  
Primary Infection ◽  
Protective Immunity ◽  
Rapid Development ◽  
Poor Responder ◽  
Post Challenge ◽  
Good Responder ◽  
Trichuris Muris ◽  
Genetically Determined

SUMMARYStrains of mice poorly (B10) or non-responsive (B10.BR) to a primary infection with Trichuris muris were protected against infection by vaccination with excretory/secretory (E/S) antigen in Complete Freund's Adjuvant (CFA). Protection in these mice was slow to be expressed compared to that in good responder strains. Vaccination boosted the IgG and IgG1 antibody responses to E/S antigen and altered the antigen recognition profiles, three high molecular weight antigens (80–85, 90–95, 105–110 kDa) being recognized by antibodies in sera from vaccinated but not control mice. B10. BR mice which had experienced a patent primary infection could not be protected against challenge infections by vaccination and this was correlated with depressed levels of IgG1, but not total IgG, to E'S antigen early post-challenge compared with vaccinated infected mice which had not seen an adult primary infection. There was also lack of recognition of the three high molecular weight antigens recognized by antibodies in sera from mice infected after vaccination. It is suggested that the rapid development of high levels of IgG1 antibodies, and the recognition of the three high molecular weight antigens, may reflect events that are important in protective immunity. Immunomodulation of host immunity by T. muris may therefore be achieved, at least in part, by the suppression of specific IgG1 levels, the production of an irrelevant IgG isotype and prevention of the recognition of critical antigens.

scholarly journals Culinary and Medicinal Mushrooms: Insight into Growing Technologies

2021 ◽  
Vol 55 (2) ◽  
Author(s):  
Piotr Zięba ◽  
Agnieszka Sękara ◽  
Katarzyna Sułkowska-Ziaja ◽  
Bożena Muszyńska
Keyword(s):  
Rapid Development ◽  
Essential Elements ◽  
Market Demand ◽  
Fruiting Bodies ◽  
Mushroom Species ◽  
Medicinal Mushrooms ◽  
Wide Range ◽  
Growing Conditions ◽  
Natural Medicines ◽  
Modern Technologies

Humans have used mushrooms from the beginning of their history. However, during the last few decades, the market demand for these fruiting bodies has increased significantly owing to the spread in the capabilities of culinary and pharmacological exploitation. Natural mushroom resources have become insufficient to meet the support needs. Therefore, traditional methods of extensive cultivation as well as modern technologies have been exploited to develop effective growing recommendations for dozens of economically important mushroom species. Mushrooms can decompose a wide range of organic materials, including organic waste. They play a fundamental role in nutrient cycling and exchange in the environment. The challenge is a proper substrate composition, including bio-fortified essential elements, and the application of growing conditions to enable a continuous supply of fruiting bodies of market quality and stabilized chemical composition. Many mushroom species are used for food preparation. Moreover, they are treated as functional foods, because they have health benefits beyond their nutritional value, and are used as natural medicines in many countries. Owing to the rapid development of mushroom farming, we reviewed the growing technologies used worldwide for mushroom species developed for food, processing, and pharmacological industries.

scholarly journals A General Fitting Function to Estimate Apparent Reaction Orders of Kinetic Profiles

2019 ◽  
Author(s):  
Robert Pollice
Keyword(s):  
Chemical Reactions ◽  
Catalyst Deactivation ◽  
Rapid Development ◽  
Product Inhibition ◽  
Time Profile ◽  
Time Data ◽  
Concentration Time ◽  
Wide Range ◽  
Reaction Orders

The rapid development of analytical methods in recent decades has resulted in a wide range of readily available and accurate reaction-monitoring techniques, which allow for easy determination of high-quality concentration-time data of chemical reactions. However, while the acquisition of kinetic data has become routine in the development of new chemical reactions and the study of their mechanisms, not all the information contained therein is utilized because of a lack of suitable analysis tools which unnecessarily complicates mechanistic studies. Herein, we report on a general method to analyze a single concentration-time profile of chemical reactions and extract information regarding the reaction order with respect to substrates, the presence of multiple kinetic regimes, and the presence of kinetic complexities, such as catalyst deactivation, product inhibition, and substrate decomposition.<br>

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