scholarly journals Novel Transcriptional and Translational Biomarkers of Tularemia Vaccine Efficacy in a Mouse Inhalation Model: Proof of Concept

2021 ◽  
Vol 10 (1) ◽  
pp. 36
Author(s):  
Qing Yan Liu ◽  
Sonia Leclerc ◽  
Youlian Pan ◽  
Ziying Liu ◽  
Felicity Stark ◽  
...  

Francisella tularensis subspecies tularensis (Ftt) is extremely virulent for humans when inhaled as a small particle aerosol (<5 µm). Inhalation of ≥20 viable bacteria is sufficient to initiate infection with a mortality rate ≥30%. Consequently, in the past, Ftt became a primary candidate for biological weapons development. To counter this threat, the USA developed a live vaccine strain (LVS), that showed efficacy in humans against inhalation of virulent Ftt. However, the breakthrough dose was fairly low, and protection waned with time. These weaknesses triggered extensive research for better vaccine candidates. Previously, we showed that deleting the clpB gene from virulent Ftt strain, SCHU S4, resulted in a mutant that was significantly less virulent than LVS for mice, yet better protected them from aerosol challenge with wild-type SCHU S4. To date, comprehensive searches for correlates of protection for SCHU S4 ΔclpB among molecules that are critical signatures of cell-mediated immunity, have yielded little reward. In this study we used transcriptomics analysis to expand the potential range of molecular correlates of protection induced by vaccination with SCHU S4 ΔclpB beyond the usual candidates. The results provide proof-of-concept that unusual host responses to vaccination can potentially serve as novel efficacy biomarkers for new tularemia vaccines.

Author(s):  
Ronald M. Baecker

Most computers during the Second World War, such as the British code-breaking Colussus machine, had been developed for military use. The effects on law and order and war and peace of computerization, worldwide telecommunications, social media, artificial intelligence (AI), and robotics is the topic of Chapter 6. As in Chapter 5, the most compelling visions of the potential opportunities and dangers have been in science fiction and in film; we begin the chapter by reviewing some memorable examples. We then discuss how technology is used by the police, such as the use of video evidence to sometimes exonerate the police against false accusations of needless brutality. We also examine how citizens are using social media to protect themselves and alert others to what they believe is unwarranted violence or unjust actions by law enforcement. We expand upon Section 5.7’s discussion of citizen mobilization by social media with the goal of regime change. In this context, we discuss how the government (especially police and security services) gains leverage via the surveillance of the digital information and communications of citizens. This surveillance has significantly increased due to security concerns post-9/11. We will examine these developments in the USA, Canada, and the UK, as well as in other parts of the world. We shall also discuss cases of organizations trying to subvert societies that repress and forbid access to the internet, with the goal of enabling its citizens to access the internet freely. Next, we consider ways in which tools of digital disruption are used by a country or government or a set of individuals against others. The timely and current case study explored is on governmental use of hacking and other aggressive digital means to interfere with the electoral processes of another country, or even to disrupt or destabilize the other country. At the extreme, governments engage in cyberterrorism or even cyberwar­fare. We shall discuss several recent examples of this and argue that weapons of cyberwar­fare could be as catastrophic as nuclear or biological weapons. The technology of warfare has also evolved.


2016 ◽  
Vol 15 (5) ◽  
pp. 24-29
Author(s):  
M. A. Sotnikova ◽  
T. B. Kravchenko ◽  
I. V. Bakhteeva ◽  
R. I. Mironova ◽  
T. I. Kombarova ◽  
...  

Relevance. Superoxide anion has bactericidal properties and is also an important inducer of proinflammatory cytokines in macrophages. We have created F. tularensis 15/sodBII strain with transiently decreased FeSOD synthesis level and more sensitive to oxidative stress. So we suggest that the modified vaccine strain have lower reactogenicity. Goal. Studying of effect of sodB gene expression modulation on biological properties of vaccine F. tularensis strain 15 NIIEG. Materials and methods. F. tularensis survival in macrophage-like cell line J774.1A and in spleen and liver of infected mice were analyzed through colony-forming unit enumeration. Strains reactogenicity was assessed by the dynamics of change in weight of infected mice. Efficacy of immune response generated by mutant strain of F. tularensis 15/sodBII was estimated with virulent F. tularensis strain Schu S4 infection in the BALB/c mice model. Results. Degree of protection was significantly more pronounced in the mice vaccinated with the strain F. tularensis with decreased sodB gene expression in comparison with parental F. tularensis strain NIIEG 15. Conclusions. The modified strain of F. tularensis 15/sodBII may be consider as a promising variant for development of a new tularemia vaccine with reduced reactogenicity.


2004 ◽  
Vol 26 (2) ◽  
pp. 15-17
Author(s):  
Jeremy Mogridge

The intentional release of Bacillus anthracis spores in the USA during the autumn of 2001 alerted the public to the possibility of future attacks using biological weapons. It also underscored the importance of understanding the pathogenesis of the organism and the need for developing new therapeutics and vaccines. Fortunately, there has been a resurgence in anthrax research. This review focuses on the characteristics of B. anthracis that have led to its use as a biological weapon and the approaches that are being taken by medical researchers to minimize the impact of another release.


2015 ◽  
Vol 22 (10) ◽  
pp. 1096-1108 ◽  
Author(s):  
Sherry L. Kurtz ◽  
Karen L. Elkins

ABSTRACTA critical hindrance to the development of a novel vaccine againstMycobacterium tuberculosisis a lack of understanding of protective correlates of immunity and of host factors involved in a successful adaptive immune response. Studies from our group and others have used a mouse-basedin vitromodel system to assess correlates of protection. Here, using this coculture system and a panel of whole-cell vaccines with varied efficacy, we developed a comprehensive approach to understand correlates of protection. We compared the gene and protein expression profiles of vaccine-generated immune peripheral blood lymphocytes (PBLs) to the profiles found in immune splenocytes. PBLs not only represent a clinically relevant cell population, but comparing the expression in these populations gave insight into compartmentally specific mechanisms of protection. Additionally, we performed a direct comparison of host responses induced when immune cells were cocultured with either the vaccine strainMycobacterium bovisBCG or virulentM. tuberculosis. These comparisons revealed host-specific and bacterium-specific factors involved in protection against virulentM. tuberculosis. Most significantly, we identified a set of 13 core molecules induced in the most protective vaccines under all of the conditions tested. Further validation of this panel of mediators as a predictor of vaccine efficacy will facilitate vaccine development, and determining how each promotes adaptive immunity will advance our understanding of antimycobacterial immune responses.


2018 ◽  
Vol 118 (5) ◽  
pp. 413-430 ◽  
Author(s):  
Ryan Chesnut ◽  
Jennifer M. DiNallo ◽  
Melina T. Czymoniewicz-Klippel ◽  
Daniel F. Perkins

Purpose Parent-focused interventions (PFIs) are a promising method for supporting parents and promoting children’s well-being. Few PFIs in the USA, however, include physical health promotion content and are universal programs. The purpose of this paper is to describe a universal health-promoting PFI for parents of elementary school-aged children and demonstrate proof of concept. Design/methodology/approach The program emphasizes positive parenting practices, stress management skills and physical health promotion strategies and recommendations, and is part of a larger initiative that includes a continuum of universal, developmentally appropriate, health-promoting PFIs for civilian and military parents. The program was implemented at two community sites in rural Pennsylvania with 20 civilian parents completing pretests and posttests. Study measures assessed parenting, stress and stress management and physical health promotion related outcomes. Findings Parents reported decreases in suboptimal discipline and feeding practices, stress and child internalizing behavior. They also reported increases in their sense of control in managing child behavior, coping socialization, child’s outdoor playtime and health recommendations met. Research limitations/implications While these preliminary findings may not be generalizable, they serve as proof of concept, which suggests that more rigorous research on the program is warranted. Practical implications Implementing a universal, health-promoting PFI within the USA is viable and has the potential to impact multiple short-term outcomes. Originality/value Parents are among their child’s earliest and most influential educators, and this study lends further support to their role as health educators. Given the significant public health benefits of holistically promoting child health, the time has come for universal PFIs to begin including physical health promotion content.


2021 ◽  
Vol 38 (1) ◽  
pp. 132-136
Author(s):  
U. Yahaya ◽  
M. Akram ◽  
R.I. Abdullahi ◽  
B.O. Adaaja ◽  
G. Otiwa ◽  
...  

The knowledge of biotechnology plays an important role in the development of biological weapons. Biological weapons are considered an attractive factor in war for several reasons: ease of manufacture, low cost, confirmed injury, increased number of victims, large losses incurred by other countries. Biological weapons detection methods are among the most important means of military defense. Biological sensors are used in early detection of weapons. Biotechnology is of paramount importance in all fields of medicine, engineering, agriculture, industry, as well as military life. The key applications of biotechnology in the military are in the areas of sensor systems and systems for protection from espionage. Among the most important countries that have applied knowledge of bioweapons technology into their security system are the USA and China. Despite the enormous advantages of biotechnology, it has negative effects in biological weapon production. Therefore, the near future will witness a tremendous boom in biotechnology. DNA profiling also plays an important role in detection of crime. The overall aim of the review is to emphasize the importance of biotechnology towards solving bioterrorism and other forms of security challenges in an environment.


2020 ◽  
Vol 14 (1) ◽  
pp. 45-46
Author(s):  
Mohamed F. Allam ◽  
Ghada E.EL-D. Amin

A recent article by Jop de Vrieze (March 23, 2020) suggested that BCG vaccine could protect against COVID-19 infections. The arguments were that several European countries, like Italy, Spain, France, and Germany, which are badly affected by COVID-19, and the USA stopped vaccination of the general population by BCG and excluded it from their routine vaccination schedule. Many people started to receive doses of BCG based on that hypothesis even before its confirmation. We think that the BCG vaccine could not protect against COVID-19 because several countries like China and Iran, which are severely affected by COVID-19, still include the BCG vaccine in its routine vaccination schedule. Other arguments include that the BCG vaccine improves cell-mediated immunity with little effect on humoral immunity; Immunity against viruses, in general, is mainly humoral.


2001 ◽  
Vol 69 (5) ◽  
pp. 3451-3454 ◽  
Author(s):  
Kathleen A. Kelly ◽  
Heather L. Gray ◽  
Jennifer C. Walker ◽  
Roger G. Rank ◽  
Floyd L. Wormley ◽  
...  

ABSTRACT Although Th1-type cell-mediated immunity (CMI) is the predominant host defense mechanism against mucosal Candida albicansinfection, CMI against a vaginal C. albicans infection in mice is limited at the vaginal mucosa despite a strongCandida-specific Th1-type response in the draining lymph nodes. In contrast, Th1-type CMI is highly effective against an experimental Chlamydia trachomatis genital tract infection. This study demonstrated through two independent designs that a concurrent Candida and Chlamydia infection could not accelerate or modulate the anti-Candida CMI response. Together, these results suggest that host responses to these genital tract infections are independent and not influenced by the presence of the other.


Insects ◽  
2022 ◽  
Vol 13 (1) ◽  
pp. 52
Author(s):  
Marina J. Orlova-Bienkowskaja ◽  
Andrzej O. Bieńkowski

Emerald ash borer Agrilus planipennis (Coleoptera: Buprestidae) is one of 20 priority quarantine pests of the European Union. It is native to Asia and is established in the USA, Canada, European Russia, and Ukraine. We made the first prognosis of the potential range of A. planipennis in Europe based on heat availability. Mean annual growing degree days base 10 °C (AGDD10) was calculated for each grid square (0.25° × 0.25° latitude x longitude degrees) on the Earth’s surface. Minimal AGDD10 recorded in the grid squares currently occupied by A. planipennis was 714° in Asia, 705° in North America, and 711° in European Russia. Agrilus planipennis has never been recorded in localities with AGDD10 below 700°. If the phenotypic plasticity would not allow this species to overcome this threshold, cold regions of Europe would probably not be invaded by A. planipennis. Thus, Fraxinus excelsior could potentially escape from A. planipennis in some regions of Norway, Sweden, Finland, Ireland, and Great Britain.


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