scholarly journals Recombinant subunit vaccines for soil-transmitted helminths

Parasitology ◽  
2017 ◽  
Vol 144 (14) ◽  
pp. 1845-1870 ◽  
Author(s):  
JASON B. NOON ◽  
RAFFI V. AROIAN

SUMMARYSoil-transmitted helminths (STHs) collectively infect one fourth of all human beings, and the majority of livestock in the developing world. These gastrointestinal nematodes are the most important parasites on earth with regard to their prevalence in humans and livestock. Current anthelmintic drugs are losing their efficacies due to increasing drug resistance, particularly in STHs of livestock and drug treatment is often followed by rapid reinfection due to failure of the immune system to develop a protective response. Vaccines against STHs offer what drugs cannot accomplish alone. Because such vaccines would have to be produced on such a large scale, and be cost effective, recombinant subunit vaccines that include a minimum number of proteins produced in relatively simple and inexpensive expression systems are required. Here, we summarize all of the previous studies pertaining to recombinant subunit vaccines for STHs of humans and livestock with the goal of both informing the public of just how critical these parasites are, and to help guide future developments. We also discuss several key areas of vaccine development, which we believe to be critical for developing more potent recombinant subunit vaccines with broad-spectrum protection.

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1072
Author(s):  
Raquel Cid ◽  
Jorge Bolívar

To date, vaccination has become one of the most effective strategies to control and reduce infectious diseases, preventing millions of deaths worldwide. The earliest vaccines were developed as live-attenuated or inactivated pathogens, and, although they still represent the most extended human vaccine types, they also face some issues, such as the potential to revert to a pathogenic form of live-attenuated formulations or the weaker immune response associated with inactivated vaccines. Advances in genetic engineering have enabled improvements in vaccine design and strategies, such as recombinant subunit vaccines, have emerged, expanding the number of diseases that can be prevented. Moreover, antigen display systems such as VLPs or those designed by nanotechnology have improved the efficacy of subunit vaccines. Platforms for the production of recombinant vaccines have also evolved from the first hosts, Escherichia coli and Saccharomyces cerevisiae, to insect or mammalian cells. Traditional bacterial and yeast systems have been improved by engineering and new systems based on plants or insect larvae have emerged as alternative, low-cost platforms. Vaccine development is still time-consuming and costly, and alternative systems that can offer cost-effective and faster processes are demanding to address infectious diseases that still do not have a treatment and to face possible future pandemics.


Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 390
Author(s):  
Frank Kowalzik ◽  
Daniel Schreiner ◽  
Christian Jensen ◽  
Daniel Teschner ◽  
Stephan Gehring ◽  
...  

Increases in the world’s population and population density promote the spread of emerging pathogens. Vaccines are the most cost-effective means of preventing this spread. Traditional methods used to identify and produce new vaccines are not adequate, in most instances, to ensure global protection. New technologies are urgently needed to expedite large scale vaccine development. mRNA-based vaccines promise to meet this need. mRNA-based vaccines exhibit a number of potential advantages relative to conventional vaccines, namely they (1) involve neither infectious elements nor a risk of stable integration into the host cell genome; (2) generate humoral and cell-mediated immunity; (3) are well-tolerated by healthy individuals; and (4) are less expensive and produced more rapidly by processes that are readily standardized and scaled-up, improving responsiveness to large emerging outbreaks. Multiple mRNA vaccine platforms have demonstrated efficacy in preventing infectious diseases and treating several types of cancers in humans as well as animal models. This review describes the factors that contribute to maximizing the production of effective mRNA vaccine transcripts and delivery systems, and the clinical applications are discussed in detail.


2014 ◽  
Vol 61 (3) ◽  
Author(s):  
Patrycja Redkiewicz ◽  
Agnieszka Sirko ◽  
Katarzyna Anna Kamel ◽  
Anna Góra-Sochacka

Many examples of a successful application of plant-based expression systems for production of biologically active recombinant proteins exist in the literature. These systems can function as inexpensive platforms for the large scale production of recombinant pharmaceuticals or subunit vaccines. Hemagglutinin (HA) is a major surface antigen of the influenza virus, thus it is in the centre of interests of various subunit vaccine engineering programs. Large scale production of recombinant HA in traditional expression systems, such as mammalian or insect cells, besides other limitations, is expensive and time-consuming. These difficulties stimulate an ever-increasing interest in plant-based production of this recombinant protein. Over the last few years many successful cases of HA production in plants, using both transient and stable expression systems have been reported. Various forms of recombinant HA, including monomers, trimers, virus like particles (VLPs) or chimeric proteins containing its fusion with other polypeptides were obtained and shown to maintain a proper antigenicity. Immunizations of animals (mice, ferrets, rabbits or chickens) with some of these plant-derived hemagglutinin variants were performed, and their effectiveness in induction of immunological response and protection against lethal challenge with influenza virus demonstrated. Plant-produced recombinant subunit vaccines and plant-made VLPs were successfully tested in clinical trials (Phase I and II) that confirmed their tolerance and immunogenicity.


Vaccines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1004
Author(s):  
Kehui Zhou ◽  
Chaoqun Li ◽  
Wen Shi ◽  
Xiaodan Hu ◽  
Kutty Selva Nandakumar ◽  
...  

Zika virus (ZIKV) is an arbovirus first discovered in the Americas. ZIKV infection is insidious based on its mild clinical symptoms observed after infection. In Brazil, after 2015, ZIKV infection broke out on a large scale, and many infected pregnant women gave birth to babies with microcephaly. The teratogenic effects of the virus on the fetus and its effects on nerves and the immune system have attracted great attention. Currently, no specific prophylactics or therapeutics are clinically available to treat ZIKV infection. Development of a safe and effective vaccine is essential to prevent the rise of any potential pandemic. In this review, we summarize the latest research on Zika vaccine development based on different strategies, including DNA vaccines, subunit vaccines, live-attenuated vaccines, virus-vector-based vaccines, inactivated vaccines, virus-like particles (VLPs), mRNA-based vaccines, and others. We anticipate that this review will facilitate further progress toward the development of effective and safe vaccines against ZIKV infection.


2021 ◽  
Author(s):  
Alexandr S. Golota ◽  
Dmitry A. Vologzhanin ◽  
Tatyana A. Kamilova ◽  
Olga V. Shneider ◽  
Sergei G. Sherbak

Genetic variability of population may explain different individual immune responses to the SARS-CoV-2 virus. The use of genome-based technologies makes it possible to develop vaccines by optimizing target antigens. The conventional approach to the development of attenuated or inactivated vaccines sometimes fail to provide potential immunity to the target antigen and has raised safety concerns in many preclinical and clinical trials. Subunit vaccines, such as those predicted by in silico research, can overcome these difficulties. The computer modeling methodology provides the scientific community with a more complete list of immunogenic peptides, including a number of new and cross-reactive candidates. Studies conducted independently of each other with different approaches provide a high degree of confidence in the reproducibility of results. Computer forecasting plays an important role in a quick and cost-effective solution to prevent further spread and ultimately eliminate the pandemic. Most of the effort to develop vaccines and drugs against SARS-CoV-2 is directed towards the thorn glycoprotein (protein S), a major inducer of neutralizing antibodies. Several vaccines have been shown to be effective in preclinical studies and have undergone clinical trials to combat COVID-19 infection. This review presents the profile of in silico predicted immunogenic peptides of the SARS-CoV-2 virus for subsequent functional validation and vaccine development, highlights current advances in the development of subunit vaccines to combat COVID-19, taking into account the experience that has been previously achieved with SARS-CoV and MERS-CoV. Immunoinformatics techniques reduce the time and cost of developing vaccines that together can stop this new viral infection.


Author(s):  
I. Chechel'

Today, large-scale programs for the construction of general education facilities are being implement-ed in the country. The Russian architecture of general educational buildings is gradually moving away from the standard architectural solutions approved by practice. This is influenced by the condi-tions of the current stage in the development of the state and society, and the tasks for the formation of an individual and a new generation of citizens. An analysis of the works of modern Russian architects suggests that the country has begun and is steadily gaining momentum in the process of forming the architecture of a new generation of school buildings. According to the author, the process is under the influence of a number of objective conditions. They are: the need to provide cost-effective architectur-al solutions of the design documentation for the mass construction of an object of General education in Russia; the continuation of the traditions of the author's architectural design for the public sector in education and the growing influence of the architecture of the non-public (private) sector to create innovative school buildings of the new generation; the impact of the reform processes in the field of pedagogical technologies in the system of General education and in solving complex issues of security and anti-terrorist protection of the object of General education on the formation of architecture of the school building; the operation of the object of General education in Emergency situation ( pandemic) and transition to the information society in the era of digitalization,; the enforcement of Federal laws of the Russian Federation in the field of safety of object of General education. Based on the identified conditions, a new systematization of the components of the architectural concept is proposed and the principles necessary for the creation of a general education building that marks the end of time are formulated.


2021 ◽  
Author(s):  
Zhihui Ma ◽  
Shufan Wang ◽  
Xuanru Lin ◽  
Xiaohua Li ◽  
Xiaotao Han ◽  
...  

Abstract The COVID-19, which belongs to the family of Coronaviridae and is large-scale outbreak in the whole world, is a public health emergency for human beings and brings some very harmful consequences in social and economic fields. In order to modelling the COVID-19 and develop the efficient control method corresponding to the contacting distance, this paper proposes an SEIR-type epidemic model with the contacting distance between the healthy individuals and the asymptomatic or symptomatic infected individuals, and the immigration rate of the healthy individuals, since the contacting distance and the immigration rate are two critical factors which determine the transmission of the COVID-19. Firstly, the threshold contacting distance and the threshold immigration rate are obtained by analyze the dynamical behaviors of the proposed SEIR-type epidemic model in order to control the COVID-19. The effect of the contacting distance and the immigration rate on the control of the COVID-19 are revealed based on ecological and epidemiological issues. The results show that the COVID-19 will be controlled while the contacting distance between the healthy individuals and the symptomatic infected individuals is larger than the threshold value A~ and the immigration rate is smaller than the threshold value ~ d. Secondly, the sensitivity analysis is conducted and the results show that the contacting distance and the immigration rate play an important role in controlling the COVID-19. Finally, the numerical test for Wuhan city are conducted and the conclusions show that the extinct lag decreases as the the contacting distance increase or the immigration rate decrease. Our study could give some reasonable suggestions for the health officials and the public.


2021 ◽  
Author(s):  
Zhihui Ma ◽  
Shufan Wang ◽  
Xuanru Lin ◽  
Xiaohua Li ◽  
Xiaotao Han ◽  
...  

Abstract The COVID-19, which belongs to the family of Coronaviridae and is large-scale outbreak in the whole world, is a public health emergency for human beings and brings some very harmful consequences in social and economic fields. In order to modelling the COVID-19 and develop the efficient control method corresponding to the contacting distance, this paper proposes an SEIR-type epidemic model with the contacting distance between the healthy individuals and the asymptomatic or symptomatic infected individuals, and the immigration rate of the healthy individuals, since the contacting distance and the immigration rate are two critical factors which determine the transmission of the COVID-19. Firstly, the threshold contacting distance and the threshold immigration rate are obtained by analyze the dynamical behaviors of the proposed SEIR-type epidemic model in order to control the COVID-19. The effect of the contacting distance and the immigration rate on the control of the COVID-19 are revealed based on ecological and epidemiological issues. The results show that the COVID-19 will be controlled while the contacting distance between the healthy individuals and the symptomatic infected individuals is larger than the threshold value $\tilde{d}^*$ and the immigration rate is smaller than the threshold value $\tilde{A}^*$. Secondly, the sensitivity analysis is conducted and the results show that the contacting distance and the immigration rate play an important role in controlling the COVID-19. Finally, the numerical test for Wuhan city are conducted and the conclusions show that the extinct lag decreases as the the contacting distance increase or the immigration rate decrease. Our study could give some reasonable suggestions for the health officials and the public.


mBio ◽  
2020 ◽  
Vol 11 (5) ◽  
Author(s):  
J. M. Myers ◽  
A. E. Bonds ◽  
R. A. Clemons ◽  
N. A. Thapa ◽  
D. R. Simmons ◽  
...  

ABSTRACT Mycoviruses are widespread and purportedly common throughout the fungal kingdom, although most are known from hosts in the two most recently diverged phyla, Ascomycota and Basidiomycota, together called Dikarya. To augment our knowledge of mycovirus prevalence and diversity in underexplored fungi, we conducted a large-scale survey of fungi in the earlier-diverging lineages, using both culture-based and transcriptome-mining approaches to search for RNA viruses. In total, 21.6% of 333 isolates were positive for RNA mycoviruses. This is a greater proportion than expected based on previous taxonomically broad mycovirus surveys and is suggestive of a strong phylogenetic component to mycoviral infection. Our newly found viral sequences are diverse, composed of double-stranded RNA, positive-sense single-stranded RNA (ssRNA), and negative-sense ssRNA genomes and include novel lineages lacking representation in the public databases. These identified viruses could be classified into 2 orders, 5 families, and 5 genera; however, half of the viruses remain taxonomically unassigned. Further, we identified a lineage of virus-like sequences in the genomes of members of Phycomycetaceae and Mortierellales that appear to be novel genes derived from integration of a viral RNA-dependent RNA polymerase gene. The two screening methods largely agreed in their detection of viruses; thus, we suggest that the culture-based assay is a cost-effective means to quickly assess whether a laboratory culture is virally infected. This study used culture collections and publicly available transcriptomes to demonstrate that mycoviruses are abundant in laboratory cultures of early-diverging fungal lineages. The function and diversity of mycoviruses found here will help guide future studies into mycovirus origins and ecological functions. IMPORTANCE Viruses are key drivers of evolution and ecosystem function and are increasingly recognized as symbionts of fungi. Fungi in early-diverging lineages are widespread, ecologically important, and comprise the majority of the phylogenetic diversity of the kingdom. Viruses infecting early-diverging lineages of fungi have been almost entirely unstudied. In this study, we screened fungi for viruses by two alternative approaches: a classic culture-based method and by transcriptome-mining. The results of our large-scale survey demonstrate that early-diverging lineages have higher infection rates than have been previously reported in other fungal taxa and that laboratory strains worldwide are host to infections, the implications of which are unknown. The function and diversity of mycoviruses found in these basal fungal lineages will help guide future studies into mycovirus origins and their evolutionary ramifications and ecological impacts.


2020 ◽  
Author(s):  
Joshua Gallaway

This talk will discuss electrochemical impedance spectroscopy (EIS) tracking of aqueous alkaline Zn-MnO2 cells cycled at 20% depth of discharge (DOD) based on cathode capacity. Shallow cycled alkaline batteries have previously been reported as cost effective and safe options for large-scale electrical storage. Periodically collected EIS data was used to fit a full battery model based on Voigt elements, and fitted parameters were tracked over time. These were used as a real-time diagnostic to assess performance and predict future performance in advance of any degradation of the cell voltage.The cell model was based on individual electrode models developed previously by Donne and co-workers for γ-MnO2 and Hampson and McNeil for Zn. Two prismatic cell builds were compared using electrodes fabricated by two different commercial sources with identical compositions. Both cell performance and EIS response were distinctly different between the electrode sources. The model provided an acceptable fit of the experimental data in both cases, as shown in Figure 1. The parameters of the model corresponded to physical phenomena, allowing an analysis of the performance difference despite the fact that all electrode fabrication variables could not be known unless provided by the commercial sources.The combined anode and cathode interfacial models were incorporated into a transmission line porous electrode, shown in Figure 2. Each anode + cathode fit involved a combined 15 parameters, which was the minimum number of parameters that would fit data for all cells in all states of charge. Performance analysis was accomplished by comparing a) the individual parameters, b) lumped parameters such as the RC time constants and RLC Q factors, and c) features of the cycling potential such as the discharge end voltage (DEV). Use of a reference electrode with EIS has been shown to be highly dependent on electrode placement. Battery EIS also faces a challenge in that electrodes may have similar capacity, while ideally the counter electrode should be non-limiting. We will address these factors and discuss steps taken to obtain repeatable data free of inductive loops caused by capacitive coupling with current collectors and electrode tabs.


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