scholarly journals Review of global use of licensed vaccines and development of new vaccines for the prevention of pneumococcal infection

2021 ◽  
Vol 21 (4) ◽  
pp. 234-243
Author(s):  
M. V. Savkina ◽  
M. A. Krivykh ◽  
N. A. Gavrilova ◽  
L. V. Sayapina ◽  
Yu. I. Obukhov ◽  
...  

Streptococcus pneumoniae infection is the most common cause of high morbidity and mortality among children under 5 years of age, immunocompromised people, and the elderly. Despite significant success, the approved pneumococcal conjugate and polysaccharide vaccines are of limited efficacy, providing protection against a small fraction of the known pneumococcal serotypes. The rapid spread of multidrug-resistant strains exacerbates the global challenge of treating infection caused by S. pneumoniae. At the same time, the emerging new strains dictate the need to include new serotypes into vaccines. In view of this, further improvement of vaccines for the prevention of pneumococcal infections is an urgent task. The aim of this study was to review advances in the development of polysaccharide, conjugate, whole-cell pneumococcal vaccines, as well as vaccines based on protein antigens and vaccines with an antigen delivery system. Genomics and proteomics data have helped to improve approaches to the creation of polysaccharide and protein-based vaccines, as well as whole-cell vaccines with the potential for population prophylactic coverage against various pneumococcal serotypes that are not included in the licensed pneumococcal vaccines. The method of antigen delivery to the cell is of great importance in the development of vaccines. The most promising strategy for improving pneumococcal vaccines is the creation of vaccines based on bacterium-like or synthetic particles carrying several antigens, including pneumococcal surface proteins. In conclusion, it should be noted that top-priority vaccines are those that provide a wide range of protection against circulating pneumococcal serotypes and, in addition to eliciting a systemic immune response, also induce local immunity.

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 132 ◽  
Author(s):  
Malihe Masomian ◽  
Zuleeza Ahmad ◽  
Lai Ti Gew ◽  
Chit Laa Poh

Streptococcus pneumoniae is a major pathogen causing pneumonia with over 2 million deaths annually, especially in young children and the elderly. To date, at least 98 different pneumococcal capsular serotypes have been identified. Currently, the vaccines for prevention of S. pneumoniae infections are the 23-valent pneumococcal polysaccharide-based vaccine (PPV23) and the pneumococcal conjugate vaccines (PCV10 and PCV13). These vaccines only cover some pneumococcal serotypes and are unable to protect against non-vaccine serotypes and unencapsulated S. pneumoniae. This has led to a rapid increase in antibiotic-resistant non-vaccine serotypes. Hence, there is an urgent need to develop new, effective, and affordable pneumococcal vaccines, which could cover a wide range of serotypes. This review discusses the new approaches to develop effective vaccines with broad serotype coverage as well as recent development of promising pneumococcal vaccines in clinical trials. New vaccine candidates are the inactivated whole-cell vaccine strain (Δpep27ΔcomD mutant) constructed by mutations of specific genes and several protein-based S. pneumoniae vaccines using conserved pneumococcal antigens, such as lipoprotein and surface-exposed protein (PspA). Among the vaccines in Phase 3 clinical trials are the pneumococcal conjugate vaccines, PCV-15 (V114) and 20vPnC. The inactivated whole-cell and several protein-based vaccines are either in Phase 1 or 2 trials. Furthermore, the recent progress of nanoparticles that play important roles as delivery systems and adjuvants to improve the performance, as well as the immunogenicity of the nanovaccines, are reviewed.


2016 ◽  
Vol 84 (4) ◽  
pp. 894-905 ◽  
Author(s):  
Magda S. Jonczyk ◽  
Laura Escudero ◽  
Nicolas Sylvius ◽  
Martin Norman ◽  
Birgitta Henriques-Normark ◽  
...  

Inflammation is a crucial part of innate immune responses but, if imbalanced, can lead to serious clinical conditions or even death. Cytokines regulate inflammation, and studies report their impact on clinical outcome. However, host and pathogen genetic backgrounds influence cytokine production, making it difficult to evaluate which inflammatory profiles (if any) relate to improved prognosis.Streptococcus pneumoniaeis a common human pathogen associated with asymptomatic nasopharyngeal carriage. Infrequently, it can lead to a wide range of diseases with high morbidity and mortality rates. Studies show that both pneumococcal serotype and host genetic background affect the development of disease and contribute to variation in inflammatory responses. In this study, we investigated the impact of the host and pneumococcal genetic backgrounds on pulmonary cytokine responses and their relationship to animal survival. Two inbred mouse strains, BALB/c and CBA/Ca, were infected with 10 pneumococcal strains, and the concentrations of six pulmonary cytokines were measured at 6 h and 24 h postinfection. Collected data were analyzed by principal-component analysis to identify whether there is any pattern in the observed cytokine variation. Our results show that host-pneumococcus combination was at the core of observed variation in cytokine responses, yet the resulting cytokine profile discriminated only between survivors and fatalities but not mouse or pneumococcal strains used during infection. Therefore, our results indicate that although alternative inflammatory profiles are generated during pneumococcal infection, a common pattern emerged, which determined the clinical outcome of pneumococcal infections.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S233-S234
Author(s):  
Corrin Graue ◽  
Bryan H Schmitt ◽  
Amy Waggoner ◽  
Frederic Laurent ◽  
Lelia Abad ◽  
...  

Abstract Background Bone and Joint Infections (BJIs) present with non-specific symptoms that may include pain, swelling, and fever and are associated with high morbidity and significant risk of mortality. BJIs can be caused by a variety of bacteria and fungi, including anaerobes and microorganisms that can be challenging to culture or identify by traditional microbiological methods. Clinicians primarily rely on culture to identify the pathogen(s) responsible for infection. The BioFire® Bone and Joint Infection (BJI) Panel (BioFire Diagnostics, Salt Lake City, UT) is designed to detect 15 gram-positive bacteria (including seven anaerobes), 14 gram-negative bacteria (including one anaerobe), two yeast, and eight antimicrobial resistance (AMR) genes from synovial fluid specimens in about an hour. The objective of this study was to evaluate the performance of an Investigational Use Only (IUO) version of the BioFire BJI Panel compared to various reference methods. Methods Remnant synovial fluid specimens, which were collected for routine clinical care at 13 study sites in the US and Europe, underwent testing using an IUO version of the BioFire BJI Panel. Performance of this test was determined by comparison to Standard of Care (SoC) consisting of bacterial culture performed at each study site according to their routine procedures. Results A total of 1544 synovial fluid specimens were collected and tested with the BioFire BJI Panel. The majority of specimens were from knee joints (77.9%) and arthrocentesis (79.4%) was the most common collection method. Compared to SoC culture, overall sensitivity was 90.2% and specificity was 99.8%. The BioFire BJI Panel yielded a total of 268 Detected results, whereas SoC yielded a total of 215 positive results for on-panel analytes. Conclusion The BioFire BJI Panel is a sensitive, specific, and robust test for rapid detection of a wide range of analytes in synovial fluid specimens. The number of microorganisms and resistance genes included in the BioFire BJI Panel, together with a reduced time-to-result and increased diagnostic yield compared to culture, is expected to aid in the timely diagnosis and appropriate management of BJIs. Disclosures Benjamin von Bredow, PhD, BioFire (Grant/Research Support) Jennifer Dien Bard, PhD, BioFire Diagnostic (Consultant, Scientific Research Study Investigator) Bart Kensinger, PhD, BioFire Diagnostics (Employee) Benedicte Pons, PhD, bioMerieux SA (Employee) Corinne Jay, PhD, bioMerieux SA (Employee)


Metrologia ◽  
2021 ◽  
Author(s):  
Ralf D Geckeler ◽  
Matthias Schumann ◽  
Andreas Just ◽  
Michael Krause ◽  
Antti Lassila ◽  
...  

Abstract Autocollimators are versatile devices for angle metrology used in a wide range of applications in engineering and manufacturing. A modern electronic autocollimator generally features two measuring axes and can thus fully determine the surface normal of an optical surface relative to it in space. Until recently, however, the calibration capabilities of the national metrology institutes were limited to plane angles. Although it was possible to calibrate both measuring axes independently of each other, it was not feasible to determine their crosstalk if angular deflections were present in both axes simultaneously. To expand autocollimator calibrations from plane angles to spatial angles, PTB and VTT MIKES have created dedicated calibration devices which are based on different measurement principles and accomplish the task of measurand traceability in different ways. Comparing calibrations of a transfer standard makes it possible to detect systematic measurement errors of the two devices and to evaluate the validity of their uncertainty budgets. The importance of measurand traceability via calibration for a broad spectrum of autocollimator applications is one of the motivating factors behind the creation of both devices and for this comparison of the calibration capabilities of the two national metrology institutes. The latter is the focus of the work presented here.


2000 ◽  
Vol 84 (5) ◽  
pp. 2204-2216 ◽  
Author(s):  
Marc L. Belleau ◽  
Richard A. Warren

We have studied the postnatal development of the physiological characteristics of nucleus accumbens (nAcb) neurons in slices from postnatal day 1 ( P1) to P49 rats using the whole cell patch-clamp technique. The majority of neurons (102/108) were physiologically identified as medium spiny (MS) projection neurons, and only these were subjected to detailed analysis. The remaining neurons displayed characteristics suggesting that they were not MS neurons. Around the time of birth and during the first postnatal weeks, the membrane and firing characteristics of MS neurons were quite different from those observed later. These characteristics changed rapidly during the first 3 postnatal weeks, at which point they began to resemble those found in adults. Both whole cell membrane resistance and membrane time constant decreased more than fourfold during the period studied. The resting membrane potential (RMP) also changed significantly from an average of −50 mV around birth to less than −80 mV by the end of the third postnatal week. During the first postnatal week, the current-voltage relationship of all encountered MS neurons was linear over a wide range of membrane potentials above and below RMP. Through the second postnatal week, the proportion of neurons displaying inward rectification in the hyperpolarized range increased steadily and after P15, all recorded MS neurons displayed significant inward rectification. At all ages, inward rectification was blocked by extracellular cesium and tetra-ethyl ammonium and was not changed by 4-aminopyridine; this shows that inward rectification was mediated by the same currents in young and mature MS neurons. MS neurons fired single and repetitive Na+/K+ action potentials as early as P1. Spike threshold and amplitude remained constant throughout development in contrast to spike duration, which decreased significantly over the same period. Depolarizing current pulses from rest showed that immature MS neurons fired action potentials more easily than their older counterparts. Taken together, the results from the present study suggest that young and adult nAcb MS neurons integrate excitatory synaptic inputs differently because of differences in their membrane and firing properties. These findings provide important insights into signal processing within nAcb during this critical period of development.


2020 ◽  
Vol 21 (1) ◽  
pp. 94-98
Author(s):  
Nikolay V. Novikov ◽  
Svetlana V. Samchenko ◽  
Galina E. Okolnikova

Due to the active development of industries using nuclear technology, the creation of highly effective and cost-effective building materials for protection against hazardous ionizing radiation is of increasing interest. Widespread in the field of radiation-protective building materials are barite-containing concrete. The purpose of this article is to establish the prospects of their use in nuclear facilities, as well as to find ways to improve their technical and operational characteristics. For this an analysis of relevant literature and scientific research in the field of radiation-protective materials and, in particular, barite-containing concrete was carried out. The advantages of barite-containing concrete are high radiation-protective properties, environmental friendliness, high density, as well as economic indicators. The disadvantages are high susceptibility to shrinkage deformation and poor resistance to cyclic temperature effects. The addition of barite to the concrete composition allows to increase the coefficient of linear absorption of -rays of the material; also, with the proper selection of the composition, such material may have strength characteristics equal to or superior to the characteristics of concrete with standard compositions. Barite-containing materials have a wide range of applications and can be used both for the production of heavy concrete in the construction of load-bearing structures and in the creation of radiation-protective coatings for walls and floors.


Author(s):  
L.R. Girfanova ◽  
◽  
R.R. Abdyrasulova ◽  

The development of digital technologies offers a wide range of opportunities to increase production efficiency, which relies on known tools and methods that transform in modern conditions. Many researchers note that the specialization most characteristic of complex knowledge-intensive industries has high prospects and is evident in all sectors of the national economy. Its combination with cooperation and outsourcing brings momentum to the development of both individual enterprises and the industry as a whole. It has been found that in light industry, which had a developed system of specializations, the return to this practice is difficult due to significant changes in the industries related to the liquidation of large mass production enterprises and the lag in the creation of digital twins, which are the basis at the stage of production preparation. Lost in the process of transition to a market economy, large production with a complete cycle is now successfully replaced by specialized small and medium-sized production, using high-performance equipment combined with modern digital technologies. It is obvious that the garment industry has entered a new cycle of development characterized by a high degree of specialization against the background of the application of digital technologies at all stages of the product life cycle. The significant lag in the application of digital technologies at the stage of production of light industry products is overcome, especially in the transition to additive technologies. It is noted that the digital shadow complements the information digital twin, which is especially relevant from the point of view of production. The introduction of digital technologies in specialized industries allows to achieve higher productivity and payback of invested capital than in standard production, where such investment is "blurred" due to the lag of related processes of the enterprise. It has been revealed that the modern stage of development of light industry is characterized by the application of fundamentally new technologies based on the creation of a digital twin and digital shadow, which create prerequisites for industrial application of additive technologies in industry. Key words: specialization, cooperation, digitalization, development of light industry


Islamology ◽  
2019 ◽  
Vol 9 (1-2) ◽  
pp. 195
Author(s):  
Saidakbar Mukhammadaminov

The article is dedicated to the manuscript heritage of Tatar scholars held in Abu Rayhan Beruni Institute of Oriental Studies of the Academy of Sciences of Uzbekistan, one of the richest manuscript repositories in the world. Works of manuscripts of Tatar theologians such as Abdurahim Utyz-Imyani, Abu al-Nasr Qursawi, Shihabaddin Mardjani, and Hisam al-Din b. Sharaf al- Din al-Bulgari, Kamal al-Din b. Siraj al-Din al-Uribfori al-Kazani, ̒Ayn al-Din b. Jalal al-Din al-Kazani, Abu al-Sharaf Husain b. Abu Umar al- Bulgari, Muhammad Latif b. Abdulislam al-Bulgari are analyzed. Based on a review of the manuscripts, it is established that some of them have not yet been catalogued. It is argued that the works of Tatar scholars were mainly devoted to religious subjects. The role of Tatar scholars in the creation of commentaries and works on legal, medical and Sufi terms is analyzed in order to make the works accessible to a wide range of people seeking knowledge.


2019 ◽  
pp. 677-690
Author(s):  
Barbara Bogusz ◽  
Roger Sexton

Titles in the Complete series combine extracts from a wide range of primary materials with clear explanatory text to provide readers with a complete introductory resource. This chapter discusses mortgage creation. It covers the definition of a mortgage; form of a legal mortgage of a fee simple before 1926; equitable right to redeem; equity of redemption; mortgagor retaining possession; legal mortgages after 1925 where land is unregistered; legal mortgages of registered land; charge by way of legal mortgage; types of mortgages; mortgages of leases; equitable mortgage by deposit of deeds (unregistered land); equitable mortgage of registered title (deposit of land certificate); and legal and equitable mortgages after 1989.


2019 ◽  
pp. 558-580
Author(s):  
Barbara Bogusz ◽  
Roger Sexton

Titles in the Complete series combine extracts from a wide range of primary materials with clear explanatory text to provide readers with a complete introductory resource. This chapter discusses the rules on the creation of an easement. Topics covered include express grant of easements (and profits); express reservation of easements (and profits); implied grant of easements (and profits), which includes ways of necessity, intended easements, the rule in Wheeldon v Burrows and s62 of the Law of Property Act 1925; implied reservation of easements covering necessity and intended easements; exclusion of the rules providing for implied grant and reservation; compulsory purchase and the rules for implied grant; and simultaneous sales or bequests.


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