Long-term Protection Research Articles

Sustained release system from PLGA particles co-encapsulated with inactivated influenza virus with natural killer T cell agonist α-galactosylceramide

Vaccines against influenza and many other infectious diseases require multiple boosters in addition to the primary dose to improve efficacy, but this approach is not ideal for compliance. The multiple doses could potentially be replaced by sustained or pulsatile release of antigens encapsulated in degradable microparticles (MPs). The efficacy of a vaccine is improved by adding an adjuvant, which can be co-delivered from the particles to enhance immunogenicity. Here, we developed degradable poly-lactic-co-glycolic acid (PLGA) (7–17 kDa) MPs capable of sustained release of ultraviolet killed influenza virus (A/PR/8/34) (kPR8) vaccine and the natural killer T (NKT) cell agonist alpha-galactosylceramide (α-GalCer) and tested their effectiveness at providing long-term protection against influenza virus infection in mice. Multiple formulations were developed for encapsulating the virus and adjuvant separately, and in combination. The MPs exhibited sustained release of both the virus and the adjuvant lasting more than a month. Co-encapsulation significantly increased the encapsulation efficiency (EE) of the vaccine but reduced the release duration. On the other hand, co-encapsulation led to a reduction in EE for the α-GalCer and a change in release profile to a higher initial burst followed by a linear release compared to a low initial burst and slower linear release. The α-GalCer also had considerably longer release duration compared to the vaccine. Mice injected with particle formulations co-encapsulating kPR8 and α-GalCer were protected from a lethal influenza virus infection 30 weeks after vaccination. This study demonstrates that PLGA MP based vaccines are promising for providing effective vaccination and possibly for replacing multiple doses with a single injection.

Tumor-Associated Myeloid Cells Selective Delivery of a Therapeutic Tumor Nano-Vaccine for Overcoming Immune Barriers for Effective and Long-Term Cancer Immunotherapy.

Therapeutic cancer vaccines have the potential to induce regression of established tumors, eradicate microscopic residual lesions, and prevent metastasis and recurrence, but their efficacy is limited by the low antigenicity of soluble antigens and the immunosuppressive tumor-associated macrophages (TAMs) that promote tumor growth. In this study, a novel strategy is reported for overcoming these defenses: a dual-targeting nano-vaccine (NV) based on hepatitis B core antigen (HBcAg) derived virus-like particles (VLPs), N-M2T-gp100 HBc NV, equipped with both SIGNR+ dendritic cells (DCs)/TAMs-targeting ability and high-density display of tumor-associated antigen (TAA). N-M2T-gp100 HBc NVs-based immunotherapy has demonstrated an optimal interaction between tumor-associated antigens (TAAs) and the immune composition of the tumor microenvironment. In a melanoma model, N-M2T-gp100 HBc VLPs significantly reducing in situ and abscopal tumor growth, and provide long-term immune protection. This remarkable anti-tumor effect is achieved by efficiently boosting of T cells and repolarizing of M2-like TAMs. This work opens exciting avenues for the development of personalized tumor vaccines targeting not just melanoma but potentially a broad range of cancer types based on functionalized VLPs.

Duration of Protection and Humoral Immune Response in Nile Tilapia (Oreochromis niloticus L.) Vaccinated against Streptococcus agalactiae.

Streptococcosis caused by Streptococcus agalactiae (S. agalactiae) is a major bacterial disease affecting the production of Nile tilapia (Oreochromis niloticus L.), causing significant economic losses due to mortality in the growing phase. Vaccination is the most effective method for preventing streptococcosis on Nile tilapia farms. In Brazil, the major tilapia-producing regions have long production cycles (6-10 months) and harvest tilapias weighing over 900 g for fillet production. Thus, data on the duration of the humoral immune response and protection in farmed tilapia have not been reported or are poorly described. Furthermore, the efficiency of serological testing for the long-term monitoring of immune responses induced by vaccination against S. agalactiae has never been addressed. This study evaluated the duration of protection and humoral immune response induced in Nile tilapia vaccinated against S. agalactiae until 300 days post-vaccination (dpv). The immunization trial was composed of two groups: vaccinated (Vac), vaccinated intraperitoneally with a commercial vaccine, and unvaccinated (NonVac) group, injected fish with sterile saline solution. At 15, 30, 150, 180, 210, and 300 dpv, blood sampling was conducted to detect anti-S. agalactiae IgM antibodies using indirect Enzyme-Linked Immunosorbent Assay (ELISA), and the fish were challenged with pathogenic S. agalactiae to determine the duration of vaccine protection through relative percentage survival (RPS). Spearman's rank correlation was performed between the ELISA optical density (OD) of vaccinated tilapia and the duration of vaccine protection (RPS). The mean cumulative mortality in NonVac and Vac groups ranged from 65 to 90% and less than 35%, respectively. The average RPS was 71, 93, 94, 70, 86, and 67% at 15, 30, 150, 180, 210, and 300 dpv, respectively. RPS revealed that the vaccine provided protection from 15 to 300 dpv. The specific anti-S. agalactiae IgM antibody levels were significantly higher in the Vac group than that non-Vac group up to 180 dpv. The vaccinated fish exhibited significant protection for up to 10 months after vaccination. There was a positive correlation between the antibody response and RPS. This study revealed that a single dose of commercial vaccine administered to Nile tilapia can confer long-term protection against S. agalactiae and that indirect ELISA can monitor the duration of the humoral immune response for up to six months following vaccination. Finally, vaccine protection over six months can be associated with other components of the fish immune system beyond the humoral immune response by IgM antibodies.

Injectable exosome-loaded quaternized chitosan/oxidized sodium alginate hydrogel with self-healing, bioadhesive, and antibacterial properties for treating combined radiation-wound injury

The management of combined radiation-wound injury (CRWI) is a major clinical challenge owing to the delayed and prolonged wound-healing process. Moreover, the mechanisms underlying the healing of CRWI are complex, and chronic wounds can increase vulnerability to multidrug-resistant bacterial infections, vascular disease, and other adverse conditions. Although exosomes from iPSC-derived mesenchymal stem cells (iMSCs) can promote injury repair, the feasibility of encapsulating them within polysaccharide-based hydrogels to treat CRWI remains to be explored. Here, iMSC-derived exosomes were encapsulated within an injectable hydrogel (HACC/OSA) consisting of quaternized chitosan (HACC) and oxidized sodium alginate (OSA). The HACC/OSA hydrogel exhibited good self-healing properties, excellent injectability, and good biocompatibility. In mouse models of CRWI, the HACC/OSA hydrogel could form a protective barrier covering the wound. Due to the presence of quaternary ammonium salts, the hydrogel could provide long-term antimicrobial protection to the wound, which was favorable for wound healing. In addition, the hydrogel could also promote CRWI repair by stabilizing exosome release. The exosome-loaded hydrogel (HACC/OSA@Exos) significantly inhibited bacterial growth and promoted the repair of CRWI, as indicated by enhanced wound healing efficiency, rapid re-epithelialization, favorable collagen deposition, and abundant angiogenesis at the wound site. Together, the in vivo and in vitro results indicated that the exosome-loaded polysaccharide-based hydrogel (HACC/OSA@Exos) can promote the healing of CRWI and potentially serve as a valuable clinical agent for CRWI management.

A highly effective ferritin-based divalent nanoparticle vaccine shields Syrian hamsters against lethal Nipah virus.

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges.

Current Status of Poultry Recombinant Virus Vector Vaccine Development.

Inactivated and live attenuated vaccines are the mainstays of preventing viral poultry diseases. However, the development of recombinant DNA technology in recent years has enabled the generation of recombinant virus vector vaccines, which have the advantages of preventing multiple diseases simultaneously and simplifying the vaccination schedule. More importantly, some can induce a protective immune response in the presence of maternal antibodies and offer long-term immune protection. These advantages compensate for the shortcomings of traditional vaccines. This review describes the construction and characterization of primarily poultry vaccine vectors, including fowl poxvirus (FPV), fowl adenovirus (FAdV), Newcastle disease virus (NDV), Marek's disease virus (MDV), and herpesvirus of turkey (HVT). In addition, the pathogens targeted and the immunoprotective effect of different poultry recombinant virus vector vaccines are also presented. Finally, this review discusses the challenges in developing vector vaccines and proposes strategies for improving immune efficacy.

Cascade catalysis nanozyme for interfacial functionalization in combating implant infections associated with diabetes via sonodynamic therapy and adaptive immune activation

Innovative solutions are required for the intervention of implant associated infections (IAIs), especially for bone defect patients with chronic inflammatory diseases like diabetes mellitus (DM). The complex immune microenvironment of infections renders implants with direct antibacterial ability inadequate for the prolonged against of bacterial infections. Herein, a synergistic treatment strategy was presented that combined sonodynamic therapy (SDT) with adaptive immune modulation to treat IAIs in diabetes patients. A multifunctional coating was created on the surface of titanium (Ti) implants, consisting of manganese dioxide nanoflakes (MnO2 NFs) with cascade catalytic enzyme activity and a responsive degradable hydrogel containing a sonosensitizer. The reactive oxygen species (ROS) generated by glucose-hydrogen peroxide (H2O2) cascade catalysis and ultrasound (US) activation sonosensitizer helped kill bacteria and release bacterial antigens. Meanwhile, Mn2+ facilitated dendritic cells (DCs) maturation, enhancing antigen presentation to activate both cellular and humoral adaptive immunity against bacterial infections. This approach effectively eliminated bacteria in established diabetic IAIs model and activated systemic antibacterial immunity, providing long-term antibacterial protection. This study presents a non-antibiotic immunotherapeutic strategy for fighting IAIs in chronic diseases.

Digital Transformation in Jordan and Poland - Implications on the Legal Protection of Cultural Heritage and Sustainable Development

This paper aims to clarify the principles of Jordanian and Polish copyright laws applicable to the preservation of cultural heritage, and to recommend the adoption of certain policies to facilitate this task. It is meant to serve as a guide for stakeholders who deal with digital cultural heritage, directed particularly at museums, but also institutions such as libraries, archives, and art galleries. The research aims to discuss the role of copyright law in protecting cultural heritage in the face of the rapid development of ICT technologies. This includes identifying the risks and challenges associated with digital heritage, framing the relationship between authors of digital cultural content, rights holders, and institutions responsible for documenting and preserving it, and the need to establish a fair mechanism that guarantees their rights. The study aims to provide a presentation of the importance of compliance with copyright principles related to the digitization of cultural heritage and other relevant regulations in the Jordan region and the Polish legislation. The article was created as a result of international scientific cooperation in combination with an innovative view at the law-making and application processes in the era of dynamic development of science and technology. The analysis will include identification of legal acts, which aim to ensure the effective, future-oriented, and long-term protection of cultural heritage in Jordan and Poland.

Multi-strategy combined bionic coating for long-term robust protection against marine biofouling

Polyurethane-fluorinated polysiloxane (PU-FPDMS) with high-strength, high-bonding and low surface energy is synthesized as the matrix, and the PU-FPDMS/MCs/Ag marine anti-fouling coating on the surface of imitation crab shells is constructed by assembling butenolide@1,1-stilbene-modified hydrolyzed polyglycidyl methacrylate/graphene oxide microcapsules (Bu@PGMAm/GO MCs) with compact multi-shell structure and Ag nanoparticles (AgNPs) step by step on the PU-FPDMS matrix. The PU-FPDMS/MCs/Ag bionic anti-fouling coatings achieve long-term and stable anti-fouling effect under the combination of robust low-surface-energy PU-FPDMS matrix, steady-state sustained release of butenolide encapsulated by the compact multi-shell, bionic surface formed by the microcapsules and AgNPs, and the release of Ag+. The shear strength, tensile strength, and elongation at break of the PU-FPDMS/MCs/Ag are 3.53 MPa, 6.7 MPa, and 192.83 %, respectively. Its static contact angle and sliding angle are 161.8° and 3.6°, respectively. The antibacterial rate of PU-FPDMS/MCs/Ag against Escherichia coli, Staphylococcus aureus, and Candida albicans can reach 100 %. Compared with glass blank, PU, PU-FPDMS, PU-FPDMS/Ag, and PU-FPDMS/MCs, both the adhesion number and coverage percentage of chlorella adhere to PU-FPDMS/MCs/Ag are the minimum values, which are 600 cell mm–2 and 1.53 %, respectively. After 6 months of marine field test, the primer blank, PU, PU-FPDMS all show different degrees of attachment by shellfish, spirorbis, algae and other biofouling, while the PU-FPDMS/MCs/Ag coating is still not covered with biofouling, while the PU-FPDMS/MCs/Ag coatings still exhibit little attachment of marine fouling. The PU-FPDMS/MCs/Ag bionic anti-fouling coatings are expected to be widely used in the fields of anti-fouling, anti-icing, anti-fogging, drag reduction, self-cleaning, and antibacterial.

Characterization of High and Stable Yield Genotype for Maize based on Multivariate stability Analysis and Prediction of Crop Yield using Ensemble Learning Techniques

The production of maize globally surpassed the wheat and rice, because it is a staple crop in many regions of the world. Also, in addition to being directly consumed by people, maize is also used to make corn ethanol, animal food and several other products of maize, therefore the stability and high yield of maize is an extremely crucial part to promote long-term growth and food protection. This study looked at the effects of G ? E interaction on yield stability in 23 hybrids of maize in 53 distinct Indian environments. On the basis of analyses of variance, stability tests for multivariate stability parameters were carried out. In terms of all characteristics, the genotype and environment (G ? E interaction) differences were highly significant (p < 0.01), according to the pooled analysis of variance. A GGE biplot was created with the two principal components, which accounted for 66.02% and 8.51% variation in GEI for the corresponding yield per hectare. The GGE biplot and AMMI model exposed genotypes SYN916801, Bio 9682, DKC 9215, NMH 4313 as good with an indication of high mean yield and stability within the environment that were tested. By the results, we suggest breeding might boost output yield, and also the identified genotypes may be suggested for commercial farming. Also, for the creation of successful agricultural and food policy, reliable crop production estimates are essential. So, examinations were made on the machine learning techniques such as random forest and Gradient Boosting algorithm to predict crop yield responses in maize. While assessing statistical performance, GBM was found highly capable of predicting yield as compared to RF. Result showed that GBM is a good and adaptable machine learning technique for yield predictions.. KEYWORDS :Additive main effect and Multiplicative interaction, G ? E interaction, Machine learning techniques, Gradient boosting machine, Random forest.

Long-Term Protection against Virulent Newcastle Disease Virus (NDV) in Chickens Immunized with a Single Dose of Recombinant Turkey Herpesvirus Expressing NDV F Protein.

Newcastle disease (ND) is a significant infectious disease in poultry, causing substantial economic losses in developing countries. To control ND, chickens must be vaccinated multiple times a year. In order to develop an improved vaccine that provides long-term protection, the F gene from genotype VII NDV was inserted into the herpesvirus of turkey (HVT) vaccine virus using CRISPR/Cas9-mediated NHEJ repair and Cre/LoxP technology. The immunogenicity and protective efficacy of the resulting recombinant vaccines were evaluated through antibody assays and virus challenge experiments. Two recombinant vaccines, rHVT-005/006-F and rHVT-US2-F, were generated, both exhibiting growth rates comparable with those of HVT in vitro and consistently expressing the F protein. One-day-old specific pathogen-free (SPF) chickens immunized with 2000 PFU/bird of either rHVT-005/006-F or rHVT-US2-F developed robust humoral immunity and were completely protected against challenge with the NDV F48E8 strain at 4 weeks post-vaccination (wpv). Furthermore, a single dose of these vaccines provided sustained protection for at least 52 wpv. Our study identifies rHVT-005/006-F and rHVT-US2-F as promising ND vaccine candidates, offering long-term protection with a single administration. Moreover, HVT-005/006 demonstrates promise for accommodating additional foreign genes, facilitating the construction of multiplex vaccines.

Subgenomic flavivirus RNA as key target for live-attenuated vaccine development.

Live-attenuated flavivirus vaccines confer long-term protection against disease, but the design of attenuated flaviviruses does not follow a general approach. The non-coding, subgenomic flavivirus RNA (sfRNA) is produced by all flaviviruses and is an essential factor in viral pathogenesis and transmission. We argue that modulating sfRNA expression is a promising, universal strategy to finetune flavivirus attenuation for developing effective flavivirus vaccines of the future.

SARS-CoV-2-specific immune responses converge in kidney disease patients and controls with hybrid immunity

Healthy individuals with hybrid immunity, due to a SARS-CoV-2 infection prior to first vaccination, have stronger immune responses compared to those who were exclusively vaccinated. However, little is known about the characteristics of antibody, B- and T-cell responses in kidney disease patients with hybrid immunity. Here, we explored differences between kidney disease patients and controls with hybrid immunity after asymptomatic or mild coronavirus disease-2019 (COVID-19). We studied the kinetics, magnitude, breadth and phenotype of SARS-CoV-2-specific immune responses against primary mRNA-1273 vaccination in patients with chronic kidney disease or on dialysis, kidney transplant recipients, and controls with hybrid immunity. Although vaccination alone is less immunogenic in kidney disease patients, mRNA-1273 induced a robust immune response in patients with prior SARS-CoV-2 infection. In contrast, kidney disease patients with hybrid immunity develop SARS-CoV-2 antibody, B- and T-cell responses that are equally strong or stronger than controls. Phenotypic analysis showed that Spike (S)-specific B-cells varied between groups in lymph node-homing and memory phenotypes, yet S-specific T-cell responses were phenotypically consistent across groups. The heterogeneity amongst immune responses in hybrid immune kidney patients warrants further studies in larger cohorts to unravel markers of long-term protection that can be used for the design of targeted vaccine regimens.

Bimodal Effect of NKG2A Blockade on Intratumoral and Systemic CD8 T Cell Response Induced by Cancer Vaccine.

Immune check-point blockade (ICB) has revitalized cancer immunotherapy, showing unprecedented efficacy despite only a narrow number of indications and with limited long-term protection. Cancer vaccines are promising combination partners for ICB to widen the patient population profiting from these treatments. Therapeutic heterologous prime-boost vaccination with KISIMATM protein vaccine and VSV-GP-TAg oncolytic virus was shown to inflame the tumor microenvironment, promoting significant infiltration of antigen-specific CD8 T cells resulting in robust antitumoral efficacy in mouse tumor models, and clinical trials are currently ongoing. Here, we report the impact of NKG2A blockade on antitumoral CD8 T cell immune response elicited by KISIMA-VSV-GP-TAg vaccination in tumor mouse models. Combination therapy significantly reduced the amount of vaccine-induced exhausted CD8 T cells infiltrating the tumor, resulting in short-term improved tumor growth control and prolonged mouse survival, while it also influenced the establishment of systemic effector memory CD8 T cell response. Taken together, these data show a compartment-dependent effect of NKG2A blockade on cancer vaccine-induced T cell immunity, increasing intratumoral T cell efficacy and attenuating the development of peripheral effector memory CD8 T cell response.

Evaluation of Immune Characteristics and Factors Associated with Immune Response following Hepatitis B Vaccination among Ghanaian Adolescents.

WHO recommends HBV-negative babies in high-prevalence (8%) countries receive anti-HBV vaccination. Ghana initiated mass immunization in 2002, but concerns remain about vaccine effectiveness and long-term protection. We evaluated immune characteristics and factors following hepatitis B vaccination among Ghanaian adolescents who received HBV vaccines. In this longitudinal cross-sectional study, 74 participants were enrolled from the Kumasi Metropolis, Ghana. Sociodemographic and lifestyle characteristics of participants were obtained using a questionnaire. Blood samples were obtained before and after booster administration for anti-HBsAg, IL-6, and IL-10 estimations using ELISA kit (Shanghai Chemical Ltd., China). Anti-HBsAg titers ≥10 mIU/ml were considered protective. Statistical analyses were done using SPSS version 26.0 and R programming language, p < 0.05 was considered statistically significant. We found 100% seroconversion rate, with 25.7% seroprotection rate (anti-HBsAg >10 mIU/ml). Gender (p=0.009), age (p=0.001), and exercising (p=0.044) were significantly associated with seroprotection. Following booster administration, 59.4% were hyporesponders (10 ≤ anti-HBsAg titre ≤99 mIU/ml) whilst 40.6% were good responders (anti-HBsAg titre ≥100 mIU/ml). Exercise (p=0.034) was significantly associated with immune response after booster administration. Moreover, we reported significant positive correlation between cytokines [IL-6 (r = 0.817, p < 0.001) and IL-10 (r = 0.928, p < 0.001)] and anti-HBsAg titre. Approximately two thirds of adolescents vaccinated at birth lack protective levels of antibodies against hepatitis B virus. Booster vaccines could aid in mounting protective levels of anti-HBsAg. Physical exercise was negatively associated with immune response to hepatitis B vaccinations.

Improvement of UV resistance and mechanism in polypropylene wax on wood surface through maleic anhydride and β-nucleating agent modification

In China, beeswax is commonly used to protect hardwood surfaces through hot waxing, and is widely utilized in wood furniture and buildings. However, beeswax, with its low melting point and high cost, is prone to being destroyed and falling off, and has a short-term protective effect on wood under ultraviolet (UV) light. Polypropylene wax (PPW), with its low cost and high melting point, holds potential for application in wood protection. The introduction of maleic anhydride enhanced the combination of PPW and wood, resulting in excellent surface properties. Additionally, the β-nucleating agent (WBG-II) induced PPW to form β crystal structure, further enhancing the UV barrier property of the wax coating. After UV irradiation, the surface properties of the hot-waxed wood using the modified polypropylene wax exhibited minimal changes, including color, adhesion, hydrophobicity, and surface roughness. The chemical structure, crystalline structure, and surface morphology were analyzed by FTIR, XRD, and SEM to reveal the photodegradation mechanism of the surface wax coating. The results demonstrated that the co-modification of polypropylene wax by maleic anhydride and WBG-II has a positive effect on the long-term protection of wood substrate, providing a reference for wood protection, particularly for dark and precious wood, and helping to reduce deforestation.

High mobility graphene field effect transistors on flexible EVA/PET foils

Monolayer graphene is a promising material for a wide range of applications, including sensors, optoelectronics, antennas, EMR shielding, flexible electronics, and conducting electrodes. Chemical vapor deposition (CVD) of carbon atoms on a metal catalyst is the most scalable and cost-efficient method for synthesizing high-quality, large-area monolayer graphene. The usual method of transferring the CVD graphene from the catalyst to a target substrate involves a polymer carrier which is dissolved after the transfer process is completed. Due to often unavoidable damage to graphene, as well as contamination and residues, carrier mobilities are typically 1000–3000 cm2(Vs)−1 , unless complex and elaborate measures are taken. Here, we report on a simple scalable fabrication method for flexible graphene field-effect transistors that eliminates the polymer interim carrier, by laminating the graphene directly onto office lamination foils, removing the catalyst, and depositing Parylene N as a gate dielectric and encapsulation layer. The fabricated transistors show field- and Hall-effect mobilities of 7000–10 000 cm2(Vs)−1 with a residual charge-carrier density of 2×1011 1 cm−2 at room temperature. We further validate the material quality by terahertz time-domain spectroscopy and observation of the quantum Hall effect at low temperatures in a moderate magnetic field of ∼5 T. The Parylene encapsulation provides long-term stability and protection against additional lithography steps, enabling vertical device integration in multilayer electronics on a flexible platform.

Post-service analysis of the degradation and protective mechanisms of chromate-based structural aircraft coatings

The substitution of chromate-containing structural coating systems in aviation with alternatives complying with nowadays strict environmental, health and safety regulations remains a formidable challenge. This complexity is partly due to the absence of a standardized from-test-to-market methodology, including a performance comparison between chromate-containing and alternative coating systems. To address this gap, the present study delves into the identification of crucial degradation factors that merit inclusion in such a methodology. Concurrently, it investigates the protective mechanisms inherent in chromate-containing coating systems and proposes improvements that can be applied to alternative coating systems. This study entails a comprehensive post-service examination of the degradation of paint applied to an aircraft component with over 35 years of service, employing electrochemical, microscopic and spectroscopic techniques. The findings underscore the role of thermo-oxidation as a significant degradation factor in the aging process of such coatings. Furthermore, the investigation elucidates a notable phenomenon in which aluminium ions within the coating pores form an aluminium hydroxide gel onto which chromate adsorbs. This process contributes to an increase in pore resistance upon exposure to electrolyte, leading to a self-healing barrier effect within the coating. Remarkably, this self-healing mechanism continues to offer long-term protection even when the coating matrix is sub-optimally cured due to application errors. Furthermore, this study reveals that the significant changes in capacitance during immersion testing result primarily from inhibitor leaching, emphasizing the effectiveness of combining Electrochemical Impedance Spectroscopy (EIS) with Scanning Electron Microscopy (SEM) analysis for studying coating degradation.

A Synthetic Circuit Empowering Reprogrammed B Cells for Therapeutic Proteins Expression Regulated by Tumor Detection.

Cancer remains a leading cause of death worldwide, but immunotherapies hold promises to cure it by awaking the patient's immune system to provide long-term protection. Cell therapies, involving the infusion of immune cells, either directly or genetically modified, are being developed to recognize and destroy cancer cells. Here, we explored the potential of a new synthetic circuit to reprogram B cells to cure cancers. This circuit consists in a sensor (a membrane-anchored IgG1), a transducer (a fragment of the NR4A1 promoter) and an effector molecule. Upon recognition of its target, this sensor triggers signaling pathways leading to the activation of the transducer and to effector expression (here, a reporter molecule). We showed that this circuit could discriminate tumors expressing the target antigen from those that did not, in a dose dependent manner in vitro. Going further, we replaced the original membrane-anchored sensor by an immunoglobulin expression cassette that can not only be membrane-anchored but also be secreted depending on B-cell maturation status. This allowed concomitant activation of the circuit and secretion of transgenic antibodies directed against the targeted antigen. Of note, these antibodies could correctly bind their target and were recognized by FcR expressed at the surface of immune cells, which should synergically amplify the action of the effector. The potential of reprogrammed B cells remains to be assessed in vivo by implementing a therapeutic effector. In the future, B-cell reprogramming platforms should allow personalized cancer treatment by adapting both the sensor and the therapeutic effectors to patients.

Vaccines for the Elderly and Vaccination Programs in Europe and the United States.

The share of the elderly population is growing worldwide as life expectancy increases. Immunosenescence and comorbidities increase infectious diseases' morbidity and mortality in older adults. Here, we aimed to summarize the latest findings on vaccines for the elderly against herpes zoster, influenza, respiratory syncytial virus (RSV), COVID-19, and pneumococcal disease and to examine vaccine recommendation differences for this age group in Europe and the United States. PubMed was searched using the keywords "elders" and "vaccine" alongside the disease/pathogen in question and paraphrased or synonymous terms. Vaccine recommendations were also sought in the European and US Centers for Disease Control and Prevention databases. Improved vaccines, tailored for the elderly, mainly by using novel adjuvants or by increasing antigen concentration, are now available. Significant differences exist between immunization policies, especially between European countries, in terms of the recipient's age, number of doses, vaccination schedule, and implementation (mandatory or recommended). Understanding the factors that influence the immune response to vaccination in the elderly may help to design vaccines that offer long-term protection for this vulnerable age group. A consensus-based strategy in Europe could help to fill the gaps in immunization policy in the elderly, particularly regarding vaccination against RSV and pneumococcus.