Impact of Protection Level on Vertically Differentiated Two-Sided Software Platforms

This paper studies the impact of software protection level on software platforms and customers’ responses to different levels of protection. This study models the interplay between users, developers and platforms, and the impact of quality degradation in the presence and absence of competitive platforms. All price structures are affected by protection level and quality degradation level for pirated copies of software. Customers, developers, and platform reaction to the protection and quality degradation levels can be contradictory, because an increase in those parameters may benefit one side, while hindering another. The results confirm that full protection against piracy is not always the best strategy in multisided platforms, but the impact of piracy changes under different scenarios.The results show that decisions regarding optimal security strategies should be taken in a systematic manner by incorporating the perspectives of all involved parties and the important factors extracted from the market within which the platform performs, such as monopoly or competition.

Mathematical analysis of the value of constructive additives in the protective suit of the kinologist

The problems of designing a suit for full protection of a cynologist-figurant are considered. A mathematical model is proposed for optimizing the value of constructive increments for predicting and searching for a rational design of PPE for a trainer-dog handler with high ergonomic properties.

Single-Dose Vaccination of Recombinant Chimeric Newcastle Disease Virus (NDV) LaSota Vaccine Strain Expressing Infectious Bursal Disease Virus (IBDV) VP2 Gene Provides Full Protection against Genotype VII NDV and IBDV Challenge

Newcastle disease virus (NDV) and infectious bursal disease virus (IBDV) are the two most important and widespread viruses causing huge economic losses in the global poultry industry. Outbreaks of genotype VII NDV and IBDV variants in vaccinated poultry flocks call for genetically matched vaccines. In the present study, a genetic matched chimeric NDV LaSota vaccine strain expressing VP2 gene of IBDV variant, rLaS-VIIF/HN-VP2 was generated for the first time, in which both the F and HN genes of LaSota were replaced with those of the genotype VII NDV strain FJSW. The cleavage site of the FJSW strain F protein in the rLaS-VIIF/HN-VP2 genome was mutated to the avirulent motif found in LaSota. Expression of IBDV VP2 protein was confirmed by western blot. The rLaS-VIIF/HN-VP2 maintained the efficient replication ability in embryonated eggs, low pathogenicity and genetic stability comparable to that of parental LaSota virus. One dose oculonasal vaccination of one-week-old SPF chickens with rLaS-VIIF/HN-VP2 induced full protection against genotype VII NDV and IBDV lethal challenge. These results indicate that the rLaS-VIIF/HN-VP2 is a promising bivalent vaccine to prevent infections of IBDV and genotype VII NDV.

Host States’ Due Diligence Obligation Towards Foreign Investors in the Context of Rebellions and Civil Wars

Based on an analysis of State practice and case law, this article examines one basic principle of international law embodied in Article 10 of the International Law Commission’s Articles on State responsibility. In the context of an unsuccessful insurrection or civil war, the host State is responsible for its own failure to discharge its due diligence obligation to protect foreign investors in relation to acts committed by rebels, i.e. to make all efforts within its capacity to suppress an insurrection and to take all reasonable measures to prevent injurious conduct by rebels and damages from occurring. This article examines the scope and content of this ‘duty to protect’ obligation, the applicable ‘test’ and the relevant circumstances to determine whether any breach of the obligation has been committed in light of recent investment awards analysing the full protection and security clause in the context of Libya’s civil war.

Effectiveness of Vaccination Against Reported SARS-CoV-2 Infection in United States Coast Guard Personnel Between May and August 2021: A Time-Series Analysis

Background: The United States Coast Guard (CG) began voluntary use of SARS-CoV-2 vaccines under an Emergency Use Authorization on December 16, 2020. Vaccination status is monitored through a service-wide immunization registry. Active Duty and Reserve (military) CG members are required to report any new positive test for COVID-19 to a centralized database. Methods: Between May and August 2021, vaccination effectiveness (VE) against any new report of COVID-19 was calculated according to standard formulas, using registry immunization status of cases and monthly mid-point vaccine coverage data. CG members recorded as fully vaccinated with a two-dose vaccine were compared with those with any other vaccine status. Sub-analyses were also conducted according to geographic area (Atlantic vs Pacific), age, and type of vaccine received. Results: Effectiveness of full vaccination reached a peak of 89.0% in June, then declined over the rest of the study period to 62.7% in August. In July and August, steeper declines in VE were seen in the Atlantic region. The rate of breakthrough infections remained under 1% in two-dose vaccine recipients, and did not differ between those who received the Moderna or Pfizer vaccines. No hospitalizations or deaths due to COVID-19 disease were recorded in fully vaccinated Coast Guard members. Conclusions: Coincident with the national spread of the Delta variant of SARS-CoV-2, overall vaccine effectiveness among CG personnel decreased during the summer months of 2021, but continued to provide substantial protection, as well as full protection against the most serious outcomes. Policy initiatives and outreach intended to increase vaccine coverage within this and other military populations could extend the disease prevention benefits seen in this study.

Full protection against all four SARS-CoV-2 variants of concern (VOC) in hamsters requires revision of spike antigen used for vaccination.

Current licensed COVID-19 vaccines are based on antigen sequences of initial SARS-CoV-2 isolates that emerged in 2019. By mid 2021 these historical virus strains have been completely replaced by new cosmopolitan SARS-CoV-2 lineages. The ongoing pandemic has been further driven by emerging variants of concern (VOC) Alpha, Beta, Gamma and, lately predominant, Delta. These are characterized by an increased transmissibility and possible escape from naturally acquired or vaccine-induced immunity. We here show, using a YF17D-vectored first-generation COVID-19 vaccine (Sanchez-Felipe et al., 2021) and a stringent hamster challenge model (Abdelnabi et al., 2021) that the immunity elicited by a prototypic spike antigen is insufficient to provide optimal protection against the Beta VoC, urging for an antigenic update. We therefore designed an updated second-generation vaccine candidate that carries the sequence of a spike antigen that includes crucial epitopes from multiple VOCs. This vaccine candidate yielded a marked change in target antigen spectrum covered as demonstrated by (i) antigenic cartography and (ii) full protection against infection and virus-induced disease caused by any of the four VOCs (Alpha, Beta, Gamma and Delta) used for challenge. This more universal COVID-19 vaccine candidate also efficiently blocked direct transmission of VOC Delta from vaccinated infected hamsters to non-vaccinated sentinels under prolonged co-housing conditions. In conclusion, our data suggest that current first-generation COVID-19 vaccines need to be adapted to cover emerging sequence diversity of VOC to preserve vaccine efficacy and to contain virus spread at the community level.

Immunomodulatory effects of mesenchymal stem cell-conditioned media on lipopolysaccharide of Vibrio cholerae as a vaccine candidate

Background Vibrio cholerae is the causative agent of cholera, which is commonly associated with high morbidity and mortality, and presents a major challenge to healthcare systems throughout the world. Lipopolysaccharide (LPS) is required for full protection against V. cholerae but can induce inflammation and septic shock. Mesenchymal stem cells (MSCs) are currently used to treat infectious and inflammatory diseases. Therefore, this study aimed to evaluate the immune-modulating effects of the LPS‐MSC‐conditioned medium (CM) on V. cholerae LPS immunization in a murine model. Methods After preconditioning MSCs with LPS, mice were immunized intraperitoneally on days 0 and 14 with the following combinations: LPS + LPS-MSC-CM; detoxified LPS (DLPS) + MSC-CM; LPS + MSC sup; LPS; LPS-MSC-CM; MSC supernatant (MSC sup); and PBS. The mouse serum and saliva samples were collected to evaluate antibody (serum IgG and saliva IgA) and cytokine responses (TNF-α, IL-10, IL-6, TGF-β, IL-4, IL-5, and B-cell activating factor (BAFF)). Results The LPS + LPS-MSC-CM significantly increased total IgG and IgA compared to other combinations (P < 0.001). TNF-α levels, in contrast to IL-10 and TGF-β, were reduced significantly in mice receiving the LPS + LPS-MSC-CM compared to mice receiving only LPS. IL-4, IL-5, and BAFF levels significantly increased in mice receiving increased doses of LPS + LPS-MSC-CM compared to those who received only LPS. The highest vibriocidal antibody titer (1:64) was observed in LPS + LPS-MSC-CM-immunized mice and resulted in a significant improvement in survival in infant mice infected by V. cholerae O1. Conclusions The LPS-MSC-CM modulates the immune response to V. cholerae LPS by regulating inflammatory and anti-inflammatory responses and inducing vibriocidal antibodies, which protect neonate mice against V. cholerae infection.

Vaccination of pentivalent, DTP, ADS vaccine for healthy and frequently sick children

Aim. To study the formation of anti-diphtheria post-vaccination immunity in practically healthy, and frequently sick children vaccinated with pentavalent, ADTP, and ADT vaccine.Material and methods. We observed 50 practically healthy and 92 frequently sick children. All children were vaccinated three times with a pentavalent vaccine, as well as revaccination with ADTP and ADT. The formation of specific anti-diphtheria immunity was detected for all children after 6 months, after 1 year, and after 5 years. The results were interpreted according to the final value of the optical density levels of protection: basic from -0,01 to 0,1; full protection -> 0.1; long-term protection -> 1.0.Results and discussion. After 6 months the intensity of post-vaccination immunity in both practically healthy and frequently sick children was the highest: full protection (> 0.1) (45,8%), basic protection (0,01 to 0,1) (31,0%). Statistical significance decreased after a year: full protection (45,8% versus 12,1%, p <0,001), and lack of protection increased (2,6% versus 55,7%, p <0,001), which indicated to the development of unstable immunity, therefore revaccination with ADTP and ADT vaccines were performed. 5 years after revaccination specific immunity tended to increase in both healthy and often-ill children.Conclusion. To create stable and long-term immunity when using “killed” vaccines and toxoids, revaccination vaccinations are required at various times after the course of vaccination for frequently ill children, as indicated by the data of basic and complete protection.

Construction of a Quadruple Gene-deleted Vaccine Confers Complete Protective Immunity Against Emerging PRV Variant Challenge in Piglets

Background: Pseudorabies virus (PRV) causes Aujeszky’s disease or pseudorabies (PR) in pigs worldwide, which leads to heavy economic losses to the swine industry. Pigs are the natural host, meanwhile, animals such as dogs, cats, foxes, rabbits, cattle and sheep are susceptible to infection. In 2011, the emerging PRV variant led to the outbreak of PR in Bar-tha-K61-vaccinated pigs. The PR outbreaks demonstrated that the Bartha-K61 vaccine did not provide full protection against the emerging PRV variant. It is widely believed that PRV live-attenuated vaccines could control PRV infection. Methods: In this study, we developed a novel PRV live-attenuated vaccine by deleting its gI, gE, US9, and US2 genes through CRISPR/Cas9, which was named PRV GDFS-delgI/gE/US9/US2.Results: Safety experiments confirmed that PRV GDFS-delgI/gE/US9/US2 was safe for 5 to 7-day-old suckling piglets. Piglets immunized with the PRV GDFS-delgI/gE/US9/US2 vaccine did not produce PRV gE-specific antibodies but could generate PRV gB-specific antibodies and high neutralizing titers against the PRV GDFS strain (variant PRV strain) or PRV Ea strain (older PRV strain). After challenge with the emerging PRV GDFS variant, none of the piglets immunized with the PRV GDFS-delgI/gE/US9/US2 vaccine showed any clinical signs, and their rectal temperatures were normal. Moreover, the autopsy and histopathological analyses revealed that the piglets in the PRV GDFS-delgI/gE/US9/US2 vaccine group did not show apparent gross or pathological lesions. Furthermore, the piglets in the PRV GDFS-delgI/gE/US9/US2 vaccine groups did not present weight loss. According to the criteria of the OIE terrestrial manual, the results of the experiment confirmed that the PRV GDFS-delgI/gE/US9/US2 vaccine could provide full protection against the emerging PRV variant strain in piglets. Conclusions: The PRV GDFS-delgI/gE/US9/US2 strain is a potential new live-attenuated vaccine against emerging PRV variant strain infections in China.

Novel Recombinant Newcastle Disease Virus-Based In Ovo Vaccines Bypass Maternal Immunity to Provide Full Protection from Early Virulent Challenge

Newcastle disease (ND) is one of the most economically important poultry diseases. Despite intensive efforts with current vaccination programs, this disease still occurs worldwide, causing significant mortality even in vaccinated flocks. This has been partially attributed to a gap in immunity during the post-hatch period due to the presence of maternal antibodies that negatively impact the replication of the commonly used live vaccines. In ovo vaccines have multiple advantages and present an opportunity to address this problem. Currently employed in ovo ND vaccines are recombinant herpesvirus of turkeys (HVT)-vectored vaccines expressing Newcastle disease virus (NDV) antigens. Although proven efficient, these vaccines have some limitations, such as delayed immunogenicity and the inability to administer a second HVT vaccine post-hatch. The use of live ND vaccines for in ovo vaccination is currently not applicable, as these are associated with high embryo mortality. In this study, recombinant NDV-vectored experimental vaccines containing an antisense sequence of avian interleukin 4 (IL4R) and their backbones were administered in ovo at different doses in 18-day-old commercial eggs possessing high maternal antibodies titers. The hatched birds were challenged with virulent NDV at 2 weeks-of-age. Post-hatch vaccine shedding, post-challenge survival, challenge virus shedding, and humoral immune responses were evaluated at multiple timepoints. Recombinant NDV (rNDV) vaccinated birds had significantly reduced post-hatch mortality compared with the wild-type LaSota vaccine. All rNDV vaccines were able to penetrate maternal immunity and induce a strong early humoral immune response. Further, the rNDV vaccines provided protection from clinical disease and significantly decreased virus shedding after early virulent NDV challenge at two weeks post-hatch. The post-challenge hemagglutination-inhibition antibody titers in the vaccinated groups remained comparable with the pre-challenge titers, suggesting the capacity of the studied vaccines to prevent efficient replication of the challenge virus. Post-hatch survival after vaccination with the rNDV-IL4R vaccines was dose-dependent, with an increase in survival as the dose decreased. This improved survival and the dose-dependency data suggest that novel attenuated in ovo rNDV-based vaccines that are able to penetrate maternal immunity to elicit a strong immune response as early as 14 days post-hatch, resulting in high or full protection from virulent challenge, show promise as a contributor to the control of Newcastle disease.