Future research to underpin successful peste des petits ruminants virus (PPRV) eradication

Peste des petits ruminants virus (PPRV) is a significant pathogen of small ruminants and is prevalent in much of Africa, the Near and Middle East and Asia. Despite the availability of an efficacious and cheap live-attenuated vaccine, the virus has continued to spread, with its range stretching from Morocco in the west to China and Mongolia in the east. Some of the world’s poorest communities rely on small ruminant farming for subsistence and the continued endemicity of PPRV is a constant threat to their livelihoods. Moreover, PPRV’s effects on the world’s population are felt broadly across many economic, agricultural and social situations. This far-reaching impact has prompted the Food and Agriculture Organization of the United Nations (FAO) and the World Organisation for Animal Health (OIE) to develop a global strategy for the eradication of this virus and its disease. PPRV is a morbillivirus and, given the experience of these organizations in eradicating the related rinderpest virus, the eradication of PPRV should be feasible. However, there are many critical areas where basic and applied virological research concerning PPRV is lacking. The purpose of this review is to highlight areas where new research could be performed in order to guide and facilitate the eradication programme. These areas include studies on disease transmission and epidemiology, the existence of wildlife reservoirs and the development of next-generation vaccines and diagnostics. With the support of the international virology community, the successful eradication of PPRV can be achieved

Neutralization of feline immunodeficiency virus by antibodies targeting the V5 loop of Env

Neutralising antibodies (NAbs) play a vital role in vaccine-induced protection against infection with feline immunodeficiency virus (FIV). However, little is known about the appropriate presentation of neutralisation epitopes in order to induce NAbs effectively; the majority of the antibodies that are induced are directed against non-neutralising epitopes. Here, we demonstrate that a subtype B strain of FIV, designated NG4, escapes autologous NAbs but may be rendered neutralisation-sensitive following the insertion of two amino acids, Lysine and Threonine, at positions 556-557 in the fifth hypervariable (V5) loop of the envelope glycoprotein (Env). Consistent with the contribution of this motif to virus neutralisation, an additional three subtype B strains retaining both residues at the same position were also neutralised by the NG4 serum and serum from an unrelated cat (TOT1) targeted the same sequence in V5. Moreover, when the V5-loop of subtype B isolate KNG2, an isolate that was moderately resistant to neutralisation by NG4 serum, was mutated to incorporate the K-T motif, the virus was rendered sensitive to neutralisation. These data suggest that even in a polyclonal sera derived from FIV infected cats following natural infection, the primary determinant of virus neutralising activity may be represented by a single, dominant epitope in V5

Treatment of Marburg and Ebola hemorrhagic fevers: A strategy for testing new drugs and vaccines under outbreak conditions.

The filoviruses, Marburg and Ebola, have the dubious distinction of being associated with some of the highest case-fatality rates of any known infectious disease-approaching 90% in many outbreaks. In recent years, laboratory research on the filoviruses has produced treatments and vaccines that are effective in laboratory animals and that could potentially drastically reduce case-fatality rates and curtail outbreaks in humans. However, there are significant challenges in clinical testing of these products and eventual delivery to populations in need. Most cases of filovirus infection are recognized only in the setting of large outbreaks, often in the most remote and resource-poor areas of sub-Saharan Africa, with little infrastructure and few personnel experienced in clinical research. Significant political, legal, and socio-cultural barriers also exist. Here, we review the present research priorities and environment for field study of the filovirus hemorrhagic fevers and outline a strategy for future prospective clinical research on treatment and vaccine prevention

Securing circulation pharmaceutically: antiviral stockpiling and pandemic preparedness in the European Union

Governments in Europe and around the world amassed vast pharmaceutical stockpiles in anticipation of a potentially catastrophic influenza pandemic. Yet the comparatively ‘mild’ course of the 2009 H1N1 pandemic provoked considerable public controversy around those stockpiles, leading to questions about their cost–benefit profile and the commercial interests allegedly shaping their creation, as well as around their scientific evidence base. So, how did governments come to view pharmaceutical stockpiling as such an indispensable element of pandemic preparedness planning? What are the underlying security rationalities that rapidly rendered antivirals such a desirable option for government planners? Drawing upon an in-depth reading of Foucault’s notion of a ‘crisis of circulation’, this article argues that the rise of pharmaceutical stockpiling across Europe is integral to a governmental rationality of political rule that continuously seeks to anticipate myriad circulatory threats to the welfare of populations – including to their overall levels of health. Novel antiviral medications such as Tamiflu are such an attractive policy option because they could enable governments to rapidly modulate dangerous levels of (viral) circulation during a pandemic, albeit without disrupting all the other circulatory systems crucial for maintaining population welfare. Antiviral stockpiles, in other words, promise nothing less than a pharmaceutical securing of circulation itself

Leukocyte Profile of Blood of Cows at Using “Leucozav” Against Leucosis of Cattle

The development of specific medical forms for fighting against the tumor disease (cancer) of people and animals has the extremely important value. The preparation «ZG-2011» («Leucozav») was invented in 2000-2006 by research associates of SSI “State center of innovative biotechnologies” that forms in inoculated animals the specific anti-viral immunity that protects cattle from being infected by the leucosis causative agent. Analogues of this preparation in Ukraine are absent. The main aim of the study is the determination of “Leucozav” influence on morphologic parameters of blood (leukocyte profile) of clinically healthy cows and ones, infected by leucosis.The object of the study was blood of cattle (milk herd), considered as unfavorable as to leucosis.Blood samples were studied before administering “Leucozav” and after that. Serological and immunological research methods were used.At the experiment it was studied, that «Leucozav» administration to infected animals normalizes leukocytes number and the ratio of their separate forms in blood of cows. In blood samples, taken of healthy cows, the preparation administration doesn\u27t influence the leukocyte profile.This experiment gives grounds to recommend the newly created preparation«Leucozav» to cows with leucosis, because it normalizes the number of leukocytes and their ration in separate forms in blood of RID-positive cows that react positively at the immune diffusion reaction in the agar gel at the study of leucosis of cattle

Intellectual Property Management Strategies to Accelerate the Development and Access of Vaccines and Diagnostics: Case Studies on Pandemic Influenza, Malaria and SARS

Achieving global access to vaccines, diagnostics, and pharmaceuticals remains a challenge. Throughout the developing world, intellectual property (IP) constraints complicate access to critically essential medical technologies and products. Vaccines for malaria and pandemic strains of influenza, as well as diagnostic and vaccine technologies for SARS, are not only relevant to global public health but are particularly critical to the needs of developing countries. A global access solution is urgently needed. This article offers a timely case‐by‐case analysis of preliminary patent landscape surveys and formulates options via patent pools and other forms of creative IP management to accelerate development and access. The analysis of the feasibility of patent pools reveals several impediments to patent pools: these include antitrust considerations, bargaining difficulties caused by asymmetric interests and asymmetric rights among IP holders (e.g. improvement vs. foundational patents), and the difficulties of securing financial support given the significant transaction costs associated with pools. Because of the above conceptual and operational hurdles, patent pools do not appear to be a feasible way to accelerate development. Other mechanisms, however, can ameliorate IP constraints. For example, a key IP constraint related to pandemic influenza vaccines R&D appears to have been resolved when Medimmune secured the assembly of all relevant reverse genetics IP and pledged broad access. Clearly, the landscape is complex and multidimensional. Licensing systems are not the only issue. Measures must also be taken to limit regulatory hurdles and enable the swift, legal production of pandemic influenza vaccines to meet the needs of developing countries. This is why a comprehensive analysis is so necessary. From a strictly legal perspective, IP systems work through the power to exclude. However, as this study’s exploration and formulation of creative licensing strategies reveals, it is also true that IP can be structured and managed to work through the “power to include.

An overview of vaccine development for COVID-19

The COVID-19 pandemic continues to endanger world health and the economy. The causative SARS-CoV-2 coronavirus has a unique replication system. The end point of the COVID-19 pandemic is either herd immunity or widespread availability of an effective vaccine. Multiple candidate vaccines - peptide, virus-like particle, viral vectors (replicating and nonreplicating), nucleic acids (DNA or RNA), live attenuated virus, recombinant designed proteins and inactivated virus - are presently under various stages of expansion, and a small number of vaccine candidates have progressed into clinical phases. At the time of writing, three major pharmaceutical companies, namely Pfizer and Moderna, have their vaccines under mass production and administered to the public. This review aims to investigate the most critical vaccines developed for COVID-19 to date

Opportunities for conventional and in situ cancer vaccine strategies and combination with immunotherapy for gastrointestinal cancers, a review

Survival of gastrointestinal cancer remains dismal, especially for metastasized disease. For various cancers, especially melanoma and lung cancer, immunotherapy has been proven to confer survival benefits, but results for gastrointestinal cancer have been disappointing. Hence, there is substantial interest in exploring the usefulness of adaptive immune system education with respect to anti-cancer responses though vaccination. Encouragingly, even fairly non-specific approaches to vaccination and immune system stimulation, involving for instance influenza vaccines, have shown promising results, eliciting hopes that selection of specific antigens for vaccination may prove useful for at least a subset of gastrointestinal cancers. It is widely recognized that immune recognition and initiation of responses are hampered by a lack of T cell help, or by suppressive cancer-associated factors. In this review we will discuss the hurdles that limit efficacy of conventional cancer therapeutic vaccination methods (e.g., peptide vaccines, dendritic cell vaccin

The challenges of creating a universal influenza vaccine

The lack of population immunity to the periodically emerging pandemic influenza strains makes influenza infection especially dangerous. The fragmented nature of the influenza virus genome contributes to the formation of influenza virus reassortants containing genomic fragments from different strains. This mechanism is the main reason for the natural influenza virus antigenic diversity as well as for the occurrence of influenza pandemics. Vaccination is the best measure to prevent the spread of influenza infection, but the efficacy of existing vaccines is not sufficient, especially for the elderly and small children. Specific immunity, developed after disease or immunization, poorly protects against infection by influenza viruses of another subtype. In this regard, there is an urgent need for a more effective universal influenza vaccine that provides a long-lasting broad cross-protective immunity, and is able to protect against influenza A and B viruses of all known subtypes. The basic approaches to as well as challenges of creating such a vaccine are discussed in this review.The lack of population immunity to the periodically emerging pandemic influenza strains makes influenza infection especially dangerous. The fragmented nature of the influenza virus genome contributes to the formation of influenza virus reassortants containing genomic fragments from different strains. This mechanism is the main reason for the natural influenza virus antigenic diversity as well as for the occurrence of influenza pandemics. Vaccination is the best measure to prevent the spread of influenza infection, but the efficacy of existing vaccines is not sufficient, especially for the elderly and small children. Specific immunity, developed after disease or immunization, poorly protects against infection by influenza viruses of another subtype. In this regard, there is an urgent need for a more effective universal influenza vaccine that provides a long-lasting broad cross-protective immunity, and is able to protect against influenza A and B viruses of all known subtypes. The basic approaches to as well as challenges of creating such a vaccine are discussed in this review