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Over the past few decades, the world has seen a considerable uptick in the number of new and emerging infectious disease outbreaks. The development of new vaccines, vaccine technologies, and platforms are critical to enhance our preparedness for biological threats and prevent future pandemics. Viral vectors can be an important tool in the repertoire of technologies available to develop effective vaccines against new and emerging infectious diseases. In many instances, vaccines may be needed in a reactive scenario, requiring technologies than can elicit rapid and robust immune responses with a single dose. Here, we discuss how viral vector vaccines are utilized in a vaccine portfolio for priority biological threats, some of the challenges in manufacturing viral vector vaccines, the need to strengthen live virus manufacturing capabilities, and future opportunities to capitalize on the use of viral vectors to improve the sustainability of the Biomedical Advanced Research and Development Authority's vaccine portfolio. [ABSTRACT FROM AUTHOR]

Over the past few decades, the world has seen a considerable uptick in the number of new and emerging infectious disease outbreaks. The development of new vaccines, vaccine technologies, and platforms are critical to enhance our preparedness for biological threats and prevent future pandemics. Viral vectors can be an important tool in the repertoire of technologies available to develop effective vaccines against new and emerging infectious diseases. In many instances, vaccines may be needed in a reactive scenario, requiring technologies than can elicit rapid and robust immune responses with a single dose. Here, we discuss how viral vector vaccines are utilized in a vaccine portfolio for priority biological threats, some of the challenges in manufacturing viral vector vaccines, the need to strengthen live virus manufacturing capabilities, and future opportunities to capitalize on the use of viral vectors to improve the sustainability of the Biomedical Advanced Research and Development Authority’s vaccine portfolio.

ABSTRACTPulmonary anthrax caused by exposure to inhaled Bacillus anthracis, the most lethal form of anthrax disease, is a continued military and public health concern for the United States. The vaccine AV7909, consisting of the licensed anthrax drug substance AVA adjuvanted with CpG7909, induces high levels of toxin neutralizing antibodies in healthy adults using fewer doses than AVA. This study compares the ability of one- or two-dose regimens of AV7909 to induce a protective immune response in guinea pigs challenged with a lethal dose of aerosolized B. anthracis spores 6 weeks after the last vaccine dose. The results indicated that AV7909 was less effective when delivered as a single dose compared to the two-dose regimen that resulted in dose-dependent protection against death. The toxin neutralizing assay (TNA) titer and anti-PA IgG responses were proportional to the protective efficacy, with a 50% TNA neutralizing factor (NF50) greater than 0.1 associated with survival in animals receiving two doses of vaccine. The strong protection at relatively low TNA NF50 titers in this guinea pig model supports the exploration of lower doses in clinical trials to determine if these protective levels of neutralizing antibodies can be achieved in humans; however, protection with a single dose may not be feasible.

Outbreaks of viral hemorrhagic fever caused by filoviruses have become more prevalent in recent years, with outbreaks of Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV) all occurring in 2022 and 2023. While licensed vaccines are now available for EBOV, vaccine candidates for SUDV and MARV are all in preclinical or early clinical development phases. During the recent outbreak of SUDV virus disease, the Biomedical Advanced Research and Development Authority (BARDA), as part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, implemented key actions with our existing partners to advance preparedness and enable rapid response to the outbreak, while also aligning with global partners involved in the implementation of clinical trials in an outbreak setting. Beyond pre-existing plans prior to the outbreak, BARDA worked with product sponsors to expedite manufacturing of vaccine doses that could be utilized in clinical trials. While the SUDV outbreak has since ended, a new outbreak of MARV disease has emerged. It remains critical that we continue to advance a portfolio of vaccines against SUDV and MARV while also expediting manufacturing activities ahead of, or in parallel if needed, outbreaks. [ABSTRACT FROM AUTHOR]

Simple Summary: Antibiotic resistance has become one of the biggest threats to global health. The occurrence of resistance is a natural phenomenon of bacterial evolution, but their inappropriate use in humans and the environment is hastening the process at a reckless speed. The speed of developing resistance is at par or, in fact, more than the speed of novel antibiotic development. Most of the big pharmaceutical companies have left antibiotic research due to the high risk of failure and poor return on investment. Antibiotic research is mostly carried out by academic institutes and small- and medium-sized enterprises. However, they lack sufficient funds to take the compounds from early-and-mid-stage to clinical trials and market. To make this possible, several government and non-government organizations worldwide have come forward to incentivize research through push funding mechanisms. The positive impact of these mechanisms, which started around a decade ago, is now visible, with fair improvements in research pipelines in the last five years. However, a large landscape of push incentives across the globe and staggered funding across different stages of development make the process complex. Efforts in various forms are now being implemented and proposed to streamline and smoothen push funding mechanisms for reinvigorating antibiotic research. The growing need for effective antibiotics is attributed to the intrinsic ability of bacteria to develop survival mechanisms. The speed at which pathogens develop resistance is at par or even faster than the discovery of newer agents. Due to the enormous cost of developing an antibiotic and poor return on investment, big pharmaceutical companies are stepping out of the antibiotic research field, and the world is now heading towards the silent pandemic of antibiotic resistance. Lack of investment in research has further led to the anemic antibiotic pipeline. To overcome these challenges, various organizations have come forward with push funding to financially assist antibiotic developers. Although push funding has somewhat reinvigorated the dwindled field of antibiotic development by bearing the financial risks of failure, the landscape is still large and staggered. Most of the funding is funneled towards the early stages; however, to carry the promising compounds forward, equal or more funding is required formid- and late-stage research. To some extent, the complexity associated with accessing the funding mechanisms has led to their underutilization. In the present review, we discuss several major push funding mechanisms, issues in their effective utilization, recent strategies adopted, and a way forward to streamline funding in antibiotic research. [ABSTRACT FROM AUTHOR]

On March 12, 2021, the Biomedical Advanced Research and Development Authority (BARDA) sponsored a virtual market research workshop, “Partnering on Vaccines to Counter Multi-Drug Resistant Threats,” to discuss the threat of antimicrobial resistance in the context of BARDA’s mission space and the challenges encountered during the development of vaccines for specific antimicrobial resistant bacteria. The workshop convened representatives with expertise in vaccine development from government, academia, and industry. This report summarizes the presentations and subsequent discussions from the workshop and highlights existing challenges to advance the development of vaccine candidates for antimicrobial resistant pathogens, including Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus.

The COVID-19 pandemic profoundly disrupted, and, out of necessity, accelerated innovation of research and development of medical countermeasures to combat COVID-19. Although countermeasures were developed with unprecedented speed as a result of decades of long-term Federal investments in platform technologies and existing partnerships, the pandemic also revealed gaps in our preparedness and response capabilities that threaten our readiness posture. Challenges include limited federal funding that hinders sustainable development and manufacturing of, and equitable access to, medical countermeasures. Here we discuss lessons learned from the development and production efforts of medical countermeasures, such as vaccines and immunotherapeutics, to combat COVID-19. This commentary highlights some of the key gaps and challenges that must be addressed to ensure preparation for future outbreaks caused by viruses of pandemic potential.

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Outbreaks of viral hemorrhagic fever caused by filoviruses have become more prevalent in recent years, with outbreaks of Ebola virus (EBOV), Sudan virus (SUDV), and Marburg virus (MARV) all occurring in 2022 and 2023. While licensed vaccines are now available for EBOV, vaccine candidates for SUDV and MARV are all in preclinical or early clinical development phases. During the recent outbreak of SUDV virus disease, the Biomedical Advanced Research and Development Authority (BARDA), as part of the Administration for Strategic Preparedness and Response within the U.S. Department of Health and Human Services, implemented key actions with our existing partners to advance preparedness and enable rapid response to the outbreak, while also aligning with global partners involved in the implementation of clinical trials in an outbreak setting. Beyond pre-existing plans prior to the outbreak, BARDA worked with product sponsors to expedite manufacturing of vaccine doses that could be utilized in clinical trials. While the SUDV outbreak has since ended, a new outbreak of MARV disease has emerged. It remains critical that we continue to advance a portfolio of vaccines against SUDV and MARV while also expediting manufacturing activities ahead of, or in parallel if needed, outbreaks.

Filoviruses cause high-consequence infections with limited approved medical countermeasures (MCMs). MCM development is dependent upon well-characterized animal models for the assessment of antiviral agents and vaccines. Following large-scale Ebola virus (EBOV) disease outbreaks in Africa, some survivors are left with long-term sequelae and persistent virus in immune-privileged sites for many years. We report the characterization of the ferret as a model for Ebola virus infection, reproducing disease and lethality observed in humans. The onset of clinical signs is rapid, and EBOV is detected in the blood, oral, and rectal swabs and all tissues studied. We identify viral RNA in the eye (a site of immune privilege) and report on specific genomic changes in EBOV present in this structure. Thus, the ferret model has utility in testing MCMs that prevent or treat long-term EBOV persistence in immune-privileged sites. [ABSTRACT FROM AUTHOR]

The Strategic National Stockpile (SNS) serves as a repository of materiel, including medical countermeasures (MCMs), that would be used to support the national health security response to a chemical, biological, radiological, or nuclear (CBRN) incident, either natural or terrorism-related. To support and advance the SNS, the National Institutes of Health (NIH) manages targeted investigatory research portfolios, such as Countermeasures Against Chemical Terrorism (CounterACT) for chemical agents, that coordinate projects covering basic research, drug discovery, and preclinical studies. Project BioShield, managed by the Biomedical Advanced Research and Development Agency (BARDA), guides and supports academia and industry with potential MCMs through the Food & Drug Administration's approval process and ultimately supports the acquisition of successful products into the SNS. Public health emergencies such as the COVID-19 pandemic and the ever-increasing number of MCMs in the SNS present logistical and financial challenges to its maintenance. While MCMs for biological agents have been readily adopted, those for chemical agents have required sustained investments. This paper reviews the methods by which MCMs are identified and supported for inclusion in the SNS, the current status of MCMs for CBRN threats, and challenges with SNS maintenance as well as identifies persistent obstacles for MCM development and acquisition, particularly for ones focused on chemical weapons. [ABSTRACT FROM AUTHOR]

Partov (contemporary Barda) was the biggest administrative and trade-handicraft center of Caucasian Albania and in a same time center of Uti Province. Partov was built in 5th A.D by Albanian Chary Vache. It became political, religious and civil center of Caucasian Albania by the early middle age. In the early Middle Ages Barda was the political, religious and cultural center of Caucasian Albaniya and lied in the center jf important political events. The of the Albanian state is transferred from Qabala to Barda in 446. In 552 the tthrone of Albanian Catholicos was transferred from Chola to Barda, the capital of the country. Barda become a center of Chistianility expanding in the country. Barda became the capital of the Arran province, separated from the Albanian princes, and from then on it was completely under Arab control. [ABSTRACT FROM AUTHOR]

The article considers the process of formation of the cities of Aran- Barda, Shamkir, Beylagan on the background of the historical events of Azerbaijan. The period of the early Middle Ages in Aran is characterized by the appearance of city-fortresses. Urban fortifications of Aran are quadrangular in structure, which is typical for the plains. Several types can be distinguished: those that arose near the ancient cities and settlements, at the best place for defense (Shemakha arose near Khynysly, Beylagan-Paytakaran (Tezekend); citadels, which formed cities (Derbent, Barda); and built based on a unified plan simultaneously with the city (Beylagan, Shamkir). The cities of this period consisted of two parts- the citadel and shahristan. The small cities of Aran regions still play an important role in the settlement system of Azerbaijan. The process of revival of small historical cities should mainly focus on the restoration and maximum use of historical heritage. [ABSTRACT FROM AUTHOR]

This article is devoted to hypotheses about the stay of representatives of Ancient Rus in the Caspian region and related to this hypothesis of the Norman theory. It is noted that sources provide valuable recordings on the incursions of Scandinavians known by the name Rus' in the Caspian region. However, there are still some theories that call into question the origin of these facts. The goals of this article are to review the evidence of Rus' activities in this region and shed light on the interpretation of this evidence in comparison with the Norman theory. [ABSTRACT FROM AUTHOR]

The city has been the most important symbol of merciless struggle against nature in mankind history since people started to live together. Cities, as places, have been one of the most important indicators of civilizations where humans have fulfilled their needs and relationships. In the Middle Ages many new cities either newly established or developed with their own structures. A new city was founded onto the core city or around it. These cities including fairs, bazaars, places for the craftsmen became the centers of important economic activities. The city of Berde had already been a miniature and mirror of Sassanians and subsequently became a miniature and mirror of Ottoman governments. Berde was one of the important centers in terms of strategic and economic position particularly silk production. Berde has never lost its importance until Russian invasion and then Mongolian invasion. The investigation of this city which was displayed in the Middle Ages historical sources in a position of east-west route was conducted by means of literature review. The geographical position, political and cultural activities, economic status of this city were investigated and its contributions to the history of civilization were examined.

The Biomedical Advanced Research and Development Authority (BARDA) conducts the advanced research and development and procurement of vaccines, therapeutics, and diagnostics for chemical, biological, radiological, and nuclear (CBRN) threats, pandemic influenza, and emerging infectious diseases. Since its inception in 2006, BARDA has played a critical role in partnering with industry to advance candidates in development toward US Food and Drug Administration (FDA) approval and then procuring them for potential use in a public health emergency. A decade into its existence, we now reflect on how BARDA has improved the preparedness posture of the United States against CBRN threat agents. BARDA has stockpiled or is the process of stockpiling 21 products for potential use in public health emergencies. Six products have achieved FDA approval or licensure. For several threat agents, the entire repertoire of medical countermeasures that have been procured and stockpiled should serve as a substantial deterrent to their future use in an attack. [ABSTRACT FROM AUTHOR]

Bu çalışmada Barda, sinemasal anlatım özellikleri ve yapısı açısından incelenerek bu yapının 'şiddet', 'adalet', 'hukuk', 'öteki' kavramlarını anlamlandırmadaki etkisi tartışılmıştır. Film, zaman kullanımı, oyun kavramını hem içeriğe taşıması hem de oyunlu bir yapı oluşturması, dikiş (sutur) ile bu oyunlu yapıyı tamamlaması, seyircinin özdeşleşmesinin ötesine geçen ve duygudaşlıkta temellenen katılımını sağlaması, geleneksel anlatı içinde çağdaş anlatı özelliklerini taşıması gibi gerek içeriksel gerekse sinematografik kodlar üzerinden değerlendirilmeye çalışılmıştır. Filmin bu yapısal özellikleriyle seyirciyi, adalet ve hukuk kavramları karşısında ikilemde bırakarak tartıştırdığı öne sürülmüştür. Bu anlamda filmin seyirci açısından da şiddeti üretenlerle yakından bir rastlaşma/yüzleşme sağladığı düşüncesi üzerinde durulmuştur. Mekansal bağlamda şiddet, oyun-şiddet ikiliği, erkeklik kavramı bağlamında şiddet öğesinin ortaya çıkışı konuları incelenmiştir.

La armadura más famosa y emblemática de la Wallace Collection de Londres es un arnés para hombre y caballo de finales del siglo XV (inv. A.21). Desafortunadamente para la historia del arte de la armadura es también una de las más heterogéneas, compuesta en el siglo XIX con piezas procedentes de al menos otras cinco armaduras. La investigación archivística en la Wallace Collection se ha compaginado con el estudio metalográfico del Departamento de Conservación para intentar arrojar algo más de luz sobre sus orígenes.

The city has been the most important symbol of merciless struggle against nature in mankind history since people started to live together. Cities, as places, have been one of the most important indicators of civilizations where humans have fulfilled their needs and relationships. In the Middle Ages many new cities either newly established or developed with their own structures. A new city was founded onto the core city or around it. These cities including fairs, bazaars, places for the craftsmen became the centers of important economic activities. The city of Berde had already been a miniature and mirror of Sassanians and subsequently became a miniature and mirror of Ottoman governments. Berde was one of the important centers in terms of strategic and economic position particularly silk production. Berde has never lost its importance until Russian invasion and then Mongolian invasion. The investigation of this city which was displayed in the Middle Ages historical sources in a position of east-west route was conducted by means of literature review. The geographical position, political and cultural activities, economic status of this city were investigated and its contributions to the history of civilization were examined. [ABSTRACT FROM AUTHOR]

The development and regulatory approval of medical countermeasures (MCMs) for the treatment and prevention of bacterial threat agent infections will require the evaluation of products in animal models. To obtain regulatory approval, these models must accurately recapitulate aspects of human disease, including, but not necessarily limited to, route of exposure, time to disease onset, pathology, immune response, and mortality. This article focuses on the state of animal model development for 3 agents for which models are largely immature: Francisella tularensis, Burkholderia mallei, and Burkholderia pseudomallei. An overview of available models and a description of scientific and regulatory gaps are provided. [ABSTRACT FROM PUBLISHER]

During archeological excavations in Barda large quantities of glass products have been discovered, and their research suggests an existence of glassware production in this ancient city of Azerbaijan. Among these things the decorative glassware items, especially bracelets, rings and beads comprise the majority. The glass beads found in Barda were similar to those beads discovered in Kiev. The item and mold found among the archaeological monuments in Kiev, with the name of Barda master (jeweller) and place) confirms extensive economic and trade relations of Barda with the surrounding cities. It is known that Barda was the capital of Albania (Azerbaijan) in the Middle Ages (V-X centuries) and located at the center of highways connecting East-West routes. [ABSTRACT FROM AUTHOR]