Current Status and Prospects of Vaccines based on DDS Technology

The development of DDS technology has contributed critically to the unprecedentedly rapid requirement for vaccines against COVID-19. LNP-based mRNA vaccines represent a subset of emerging DDS technology. Despite the groundbreaking nature of these vaccines, they are yet to be perfected and as such, new technologies are being developed to optimize these vaccines. This review will focus on exploring one of the modalities of recombinant protein vaccines and will introduce various findings on the enhancement of vaccine efficacy using antigen modification technologies, including VLPs and Fc-fusion proteins, and adjuvant improvements.Alternate :抄録COVID-19に対してかつてない速度でワクチンが普及した背景には、DDS技術の発展が必要不可欠であった。特に、mRNAワクチンにおける脂質ナノ粒子（LNP）の開発は、まさにDDS技術の結集といえよう。一方で、mRNAワクチンを含め、現状のさまざまなワクチンは多くの課題を有しており、より効果的かつ安全なワクチン開発に資する基盤技術の確立が世界的に待望されている。本稿では、ワクチンモダリティの1つである組換えタンパク質ワクチンに焦点を絞り、抗原改変技術からアジュバントの改良に至るまで、ワクチン開発基盤技術の最新知見について紹介する。

Development of therapeutic antibodies for the treatment of infection diseases and future aspect

Since the late 1990s, therapeutic antibodies have been developed for various oncology and immunoinflammatory diseases. To date, more than 100 therapeutic antibodies have been approved in Japan, the U.S., and Europe for these indications. In contrast, the development of antibody drugs in the field of infectious diseases has been limited so far. The recent SARS-CoV-2 pandemic has highlighted the importance of therapeutic antibodies for infectious diseases as well as the development of drug delivery systems（DDS）. This review summarizes the past development of antibody drugs for infectious diseases and provides a future perspective of how therapeutic antibodies can be developed by utilizing antibody engineering and DDS technologies.Alternate :抄録1990年代後半に、がん領域や免疫炎症性疾患領域において、抗体医薬品が画期的な治療効果を示して以降、さまざまな疾患領域において抗体医薬品の研究開発がなされ、現在までに日米欧で100品目を超える抗体医薬品が承認されている。感染症領域における抗体医薬品の開発は限られていたが、抗体工学の発展、SARS-CoV-2の感染の拡大により、感染症領域における抗体医薬品の重要性が注目されている。本稿では、これまでの感染症領域における抗体医薬品の開発と、抗体工学やDDS技術の進展に伴う今後の抗体医薬品の展望を概説する。

Current Status and Prospects of Vaccines based on DDS Technology.

The development of DDS technology has contributed critically to the unprecedentedly rapid requirement for vaccines against COVID-19. LNP-based mRNA vaccines represent a subset of DDS emerging DDS technology. Despite the groundbreaking nature of these vaccines, they are yet to be perfected and as such, new technologies are being developed to optimize these vaccines. This review will focus on exploring one of the modalities of recombinant protein vaccines and will introduce various findings on the enhancement of vaccine efficacy using antigen modification technologies, including VLPs and Fc-fusion proteins, and adjuvant improvements.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Current Status and Prospects of Vaccines based on DDS Technology.

The development of DDS technology has contributed critically to the unprecedentedly rapid requirement for vaccines against COVID-19. LNP-based mRNA vaccines represent a subset of DDS emerging DDS technology. Despite the groundbreaking nature of these vaccines, they are yet to be perfected and as such, new technologies are being developed to optimize these vaccines. This review will focus on exploring one of the modalities of recombinant protein vaccines and will introduce various findings on the enhancement of vaccine efficacy using antigen modification technologies, including VLPs and Fc-fusion proteins, and adjuvant improvements.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Current Status and Prospects of Vaccines based on DDS Technology.

The development of DDS technology has contributed critically to the unprecedentedly rapid requirement for vaccines against COVID-19. LNP-based mRNA vaccines represent a subset of DDS emerging DDS technology. Despite the groundbreaking nature of these vaccines, they are yet to be perfected and as such, new technologies are being developed to optimize these vaccines. This review will focus on exploring one of the modalities of recombinant protein vaccines and will introduce various findings on the enhancement of vaccine efficacy using antigen modification technologies, including VLPs and Fc-fusion proteins, and adjuvant improvements.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Development of therapeutic antibodies for the treatment of infection diseases and future aspect.

Since the late 1990 s, therapeutic antibodies have been developed for various oncology and immunoinflammatory diseases. To date, more than 100 therapeutic antibodies have been approved DDS in Japan, the U.S., and Europe for these indications. In contrast, the development of antibody drugs in the field of infectious diseases has been limited so far. The recent SARS-CoV-2 pandemic has highlighted the importance of therapeutic antibodies for infectious diseases as well as the development of drug delivery systemsDDS. This review summarizes the past development of antibody drugs for infectious diseases and provides a future perspective of how therapeutic antibodies can be developed by utilizing antibody engineering and DDS technologies.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Development of therapeutic antibodies for the treatment of infection diseases and future aspect.

Since the late 1990 s, therapeutic antibodies have been developed for various oncology and immunoinflammatory diseases. To date, more than 100 therapeutic antibodies have been approved DDS in Japan, the U.S., and Europe for these indications. In contrast, the development of antibody drugs in the field of infectious diseases has been limited so far. The recent SARS-CoV-2 pandemic has highlighted the importance of therapeutic antibodies for infectious diseases as well as the development of drug delivery systems(DDS). This review summarizes the past development of antibody drugs for infectious diseases and provides a future perspective of how therapeutic antibodies can be developed by utilizing antibody engineering and DDS technologies.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Development of therapeutic antibodies for the treatment of infection diseases and future aspect.

Since the late 1990 s, therapeutic antibodies have been developed for various oncology and immunoinflammatory diseases. To date, more than 100 therapeutic antibodies have been approved DDS in Japan, the U.S., and Europe for these indications. In contrast, the development of antibody drugs in the field of infectious diseases has been limited so far. The recent SARS-CoV-2 pandemic has highlighted the importance of therapeutic antibodies for infectious diseases as well as the development of drug delivery systems(DDS). This review summarizes the past development of antibody drugs for infectious diseases and provides a future perspective of how therapeutic antibodies can be developed by utilizing antibody engineering and DDS technologies.Copyright © 2022, Japan Society of Drug Delivery System. All rights reserved.

Current Opinion on the Therapeutic Capacity of Taurine-Containing Halogen Derivatives in Infectious and Inflammatory Diseases.

Taurine haloamines, N-chlorotaurine (NCT, TauCl), and N-bromotaurine (NBT, TauBr) are formed by a reaction between taurine and hypohalous acids, HOCl and HOBr, respectively. The major source of endogenous taurine haloamines is neutrophils. Both NCT and NBT share strong anti-inflammatory and microbicidal activities supported by an absence of microbial resistance. In the light of these properties, a number of clinical studies have been performed to document their effectiveness in treatment of bacterial, fungal, and viral infections. The administration of NCT and NBT has been limited to topical application, as they are decomposed upon systemic delivery. This review summarizes current knowledge concerning the therapeutic use of NCT and NBT mainly in various skin disorders such as non-healing wounds, acne vulgaris, herpes zoster, and psoriasis. Moreover, the beneficial effect of NCT inhalation in early stages of COVID-19 and other viral respiratory infections is discussed. And finally, we would like to suggest that NCT might be used to inhibit the development of the cytokine storm through its capacity to suppress the production of IL-6.

Antibiotic Management of Patients with Hematologic Malignancies: From Prophylaxis to Unusual Infections.

PURPOSE OF REVIEW: Patients with hematological malignancies are recognized for their high susceptibility and increased risk of developing infections associated with immunosuppression that can be caused by the infection itself or by the treatments that condition a decrease in the humoral and T lymphocyte response, so this review attempts to gather the main bacterial, viral, parasitic, and fungal agents that affect them and give recommendations for their approach and diagnosis. RECENT FINDINGS: In recent years, with the discovery and use of new therapies including immunological and targeted treatments, it has been possible to improve the survival and response of patients with hematological malignancies; however, antimicrobial resistance has also increased; we have faced new and unknown microorganisms, such as the SARS-CoV-2 that caused the COVID-19 pandemic in the past year, and therefore, new risks and more severe infections are presented. We present a review of the different circumstances where hematological malignancies increased the risk of infections and which microorganisms affect these patients, their characteristics, and the suggested prophylaxis.

Toxicity of spike fragments SARS-CoV-2 S protein for zebrafish: A tool to study its hazardous for human health?

Despite the significant increase in the generation of SARS-CoV-2 contaminated domestic and hospital wastewater, little is known about the ecotoxicological effects of the virus or its structural components in freshwater vertebrates. In this context, this study evaluated the deleterious effects caused by SARS-CoV-2 Spike protein on the health of Danio rerio, zebrafish. We demonstrated, for the first time, that zebrafish injected with fragment 16 to 165 (rSpike), which corresponds to the N-terminal portion of the protein, presented mortalities and adverse effects on liver, kidney, ovary and brain tissues. The conserved genetic homology between zebrafish and humans might be one of the reasons for the intense toxic effects followed inflammatory reaction from the immune system of zebrafish to rSpike which provoked damage to organs in a similar pattern as happen in severe cases of COVID-19 in humans, and, resulted in 78,6% of survival rate in female adults during the first seven days. The application of spike protein in zebrafish was highly toxic that is suitable for future studies to gather valuable information about ecotoxicological impacts, as well as vaccine responses and therapeutic approaches in human medicine. Therefore, besides representing an important tool to assess the harmful effects of SARS-CoV-2 in the aquatic environment, we present the zebrafish as an animal model for translational COVID-19 research.

Duality Between Coronavirus Transmission and Air-Based Macroscopic Molecular Communication.

This contribution exploits the duality between a viral infection process and macroscopic air-based molecular communication. Airborne aerosol and droplet transmission through human respiratory processes is modeled as an instance of a multiuser molecular communication scenario employing respiratory-event-driven molecular variable-concentration shift keying. Modeling is aided by experiments that are motivated by a macroscopic air-based molecular communication testbed. In artificially induced coughs, a saturated aqueous solution containing a fluorescent dye mixed with saliva is released by an adult test person. The emitted particles are made visible by means of optical detection exploiting the fluorescent dye. The number of particles recorded is significantly higher in test series without mouth and nose protection than in those with a well-fitting medical mask. A simulation tool for macroscopic molecular communication processes is extended and used for estimating the transmission of infectious aerosols in different environments. Towards this goal, parameters obtained through self experiments are taken. The work is inspired by the recent outbreak of the coronavirus pandemic.

A knowledge-based self-pre-diagnosis system to predict Covid-19 in smartphone users using personal data and observed symptoms.

Covid-19 is an acute respiratory infection and presents various clinical features ranging from no symptoms to severe pneumonia and death. Medical expert systems, especially in diagnosis and monitoring stages, can give positive consequences in the struggle against Covid-19. In this study, a rule-based expert system is designed as a predictive tool in self-pre-diagnosis of Covid-19. The potential users are smartphone users, healthcare experts and government health authorities. The system does not only share the data gathered from the users with experts, but also analyzes the symptom data as a diagnostic assistant to predict possible Covid-19 risk. To do this, a user needs to fill out a patient examination card that conducts an online Covid-19 diagnostic test, to receive an unconfirmed online test prediction result and a set of precautionary and supportive action suggestions. The system was tested for 169 positive cases. The results produced by the system were compared with the real PCR test results for the same cases. For patients with certain symptomatic findings, there was no significant difference found between the results of the system and the confirmed test results with PCR test. Furthermore, a set of suitable suggestions produced by the system were compared with the written suggestions of a collaborated health expert. The suggestions deduced and the written suggestions of the health expert were similar and the system suggestions in line with suggestions of the expert. The system can be suitable for diagnosing and monitoring of positive cases in the areas other than clinics and hospitals during the Covid-19 pandemic. The results of the case studies are promising, and it demonstrates the applicability, effectiveness, and efficiency of the proposed approach in all communities.

Coronavirus Disease 2019-Liver Injury-Literature Review and Guidelines Based on the Recommendations of Hepatological Societies.

The aim of our paper was to present current knowledge, review literature and available practice guidelines of international hepatological associations regarding the effect of severe acute respiratory syndrome coronavirus 2 coronavirus on the liver, patients with underline liver disease, awaiting on liver transplantation (LTx) or being after LTx in the pandemic coronavirus disease 2019 area.

Using in silico modelling and FRET-based assays in the discovery of novel FDA-approved drugs as inhibitors of MERS-CoV helicase.

A Förster resonance energy transfer (FRET)-based assay was used to screen the FDA-approved compound library against the MERS-CoV helicase, an essential enzyme for virus replication within the host cell. Five compounds inhibited the helicase activity with submicromolar potencies (IC50, 0.73-1.65 µM) and ten compounds inhibited the enzyme with micromolar potencies (IC50, 19.6-502 µM). The molecular operating environment (MOE) was used to dock the identified inhibitors on the MERS-CoV helicase nucleotide binding. Strong inhibitors docked well in the nucleotide-binding site and established interactions with some of the essential residues. There was a reasonable correlation between the observed IC50 values and the MOE docking scores of the strong inhibitors (r 2 = 0.74), indicating the ability of the in silico docking model to predict the binding of strong inhibitors. In silico docking could be a useful complementary tool used with the FRET-based assay to predict new MERS-CoV helicase inhibitors. The identified inhibitors could potentially be used in the clinical development of new antiviral treatment for MERS-CoV and other coronavirus related diseases, including coronavirus disease 2019 (COVID-19).

Impact on disease mortality of clinical, biological, and virological characteristics at hospital admission and overtime in COVID-19 patients.

Little is known on the association between clinical factors and coronavirus disease 2019 (COVID-19) more than 15 days after diagnosis. We conducted a multicentric prospective cohort of COVID-19 hospitalized patients to describe clinical, biological, and virological characteristics at hospital admission and over time, according to mortality up to Day 60 after admission. For the analysis of risk factors of survival, analyses assessing associations between mortality and demographic characteristics or comorbidities were performed using a Cox regression model. Between January 24 and March 15, 2020, 246 patients with reverse-transcriptase polymerase chain reactions virologically confirmed COVID-19 were enrolled. In multivariate analysis, mortality at Day 60 (n = 42 patients, 17.1% [95% confidence interval, 12.6-22.4]) was associated with older age (adjusted hazard ratio [aHR] for age ≥ 65 years: 5.22 [2.56-10.63, p < .001]), gender (aHR for male: 2.97 [1.47-5.99, p = .002]), chronic pulmonary disease (aHR: 4.84 [2.32-10.07, p < .001]), obesity (aHR: 3.32 [1.70-6.52, p < .001]), and diabetes (aHR: 1.98 [1.01-3.89, p = .048]). The median nasopharyngeal viral load at admission was 6.4 log10 copies/ml and was associated with mortality regardless of clinical risk factors. Viral load decreased with time elapsed since symptoms onset. Our study confirmed that mortality was associated with clinical characteristics at admission. The viral load at admission was significantly lower in patients admitted late after the onset of symptoms in both dead and alive patients. Our results could improve earlier identification of patients with increased risk of mortality and adapted management.

Nano-based approaches in the development of antiviral agents and vaccines.

Outbreaks and the rapid transmission of viruses, such as coronaviruses and influenza viruses, are serious threats to human health. A major challenge in combating infectious diseases caused by viruses is the lack of effective methods for prevention and treatment. Nanotechnology has provided a basis for the development of novel antiviral strategies. Owing to their large modifiable surfaces that can be functionalized with multiple molecules to realize sophisticated designs, nanomaterials have been developed as nanodrugs, nanocarriers, and nano-based vaccines to effectively induce sufficient immunologic memory. From this perspective, we introduce various nanomaterials with diverse antiviral mechanisms and summarize how nano-based antiviral agents protect against viral infection at the molecular, cellular, and organismal levels. We summarize the applications of nanomaterials for defense against emerging viruses by trapping and inactivating viruses and inhibiting viral entry and replication. We also discuss recent progress in nano-based vaccines with a focus on the mechanisms by which nanomaterials contribute to immunogenicity. We further describe how nanotechnology may improve vaccine efficacy by delivering large amounts of antigens to target immune cells and enhancing the immune response by mimicking viral structures and activating dendritic cells. Finally, we provide an overview of future prospects for nano-based antiviral agents and vaccines.

Contactless Vital Signs Measurement System Using RGB-Thermal Image Sensors and Its Clinical Screening Test on Patients with Seasonal Influenza.

Background: In the last two decades, infrared thermography (IRT) has been applied in quarantine stations for the screening of patients with suspected infectious disease. However, the fever-based screening procedure employing IRT suffers from low sensitivity, because monitoring body temperature alone is insufficient for detecting infected patients. To overcome the drawbacks of fever-based screening, this study aims to develop and evaluate a multiple vital sign (i.e., body temperature, heart rate and respiration rate) measurement system using RGB-thermal image sensors. Methods: The RGB camera measures blood volume pulse (BVP) through variations in the light absorption from human facial areas. IRT is used to estimate the respiration rate by measuring the change in temperature near the nostrils or mouth accompanying respiration. To enable a stable and reliable system, the following image and signal processing methods were proposed and implemented: (1) an RGB-thermal image fusion approach to achieve highly reliable facial region-of-interest tracking, (2) a heart rate estimation method including a tapered window for reducing noise caused by the face tracker, reconstruction of a BVP signal with three RGB channels to optimize a linear function, thereby improving the signal-to-noise ratio and multiple signal classification (MUSIC) algorithm for estimating the pseudo-spectrum from limited time-domain BVP signals within 15 s and (3) a respiration rate estimation method implementing nasal or oral breathing signal selection based on signal quality index for stable measurement and MUSIC algorithm for rapid measurement. We tested the system on 22 healthy subjects and 28 patients with seasonal influenza, using the support vector machine (SVM) classification method. Results: The body temperature, heart rate and respiration rate measured in a non-contact manner were highly similarity to those measured via contact-type reference devices (i.e., thermometer, ECG and respiration belt), with Pearson correlation coefficients of 0.71, 0.87 and 0.87, respectively. Moreover, the optimized SVM model with three vital signs yielded sensitivity and specificity values of 85.7% and 90.1%, respectively. Conclusion: For contactless vital sign measurement, the system achieved a performance similar to that of the reference devices. The multiple vital sign-based screening achieved higher sensitivity than fever-based screening. Thus, this system represents a promising alternative for further quarantine procedures to prevent the spread of infectious diseases.