Computational design of novel chimeric multiepitope vaccine against bacterial and viral disease in tilapia (Oreochromis sp.).

Regarding several infectious diseases in fish, multiple vaccinations are not favorable. The chimeric multiepitope vaccine (CMEV) harboring several antigens for multi-disease prevention would enhance vaccine efficiency in terms of multiple disease prevention. Herein, the immunogens of tilapia's seven pathogens including E. tarda, F. columnare, F. noatunensis, S. iniae, S. agalactiae, A. hydrophila, and TiLV were used for CMEV design. After shuffling and annotating the B-cell epitopes, 5,040 CMEV primary protein structures were obtained. Secondary and tertiary protein structures were predicted by AlphaFold2 creating 25,200 CMEV. Proper amino acid alignment in the secondary structures was achieved by the Ramachandran plot. In silico determination of physiochemical and other properties including allergenicity, antigenicity, glycosylation, and conformational B-cell epitopes were determined. The selected CMEV (OSLM0467, OSLM2629, and OSLM4294) showed a predicted molecular weight (MW) of 70 kDa, with feasible sites of N- and O-glycosylation, and a number of potentially conformational B-cell epitope residues. Molecular docking, codon optimization, and in-silico cloning were tested to evaluate the possibility of protein expression. Those CMEVs will further elucidate in vitro and in vivo to evaluate the efficacy and specific immune response. This research will highlight the new era of vaccines designed based on in silico structural vaccine design.

Protein Nanoparticles as Vaccine Platforms for Human and Zoonotic Viruses.

Vaccines are one of the most effective medical interventions, playing a pivotal role in treating infectious diseases. Although traditional vaccines comprise killed, inactivated, or live-attenuated pathogens that have resulted in protective immune responses, the negative consequences of their administration have been well appreciated. Modern vaccines have evolved to contain purified antigenic subunits, epitopes, or antigen-encoding mRNAs, rendering them relatively safe. However, reduced humoral and cellular responses pose major challenges to these subunit vaccines. Protein nanoparticle (PNP)-based vaccines have garnered substantial interest in recent years for their ability to present a repetitive array of antigens for improving immunogenicity and enhancing protective responses. Discovery and characterisation of naturally occurring PNPs from various living organisms such as bacteria, archaea, viruses, insects, and eukaryotes, as well as computationally designed structures and approaches to link antigens to the PNPs, have paved the way for unprecedented advances in the field of vaccine technology. In this review, we focus on some of the widely used naturally occurring and optimally designed PNPs for their suitability as promising vaccine platforms for displaying native-like antigens from human viral pathogens for protective immune responses. Such platforms hold great promise in combating emerging and re-emerging infectious viral diseases and enhancing vaccine efficacy and safety.

Does Prior Respiratory Viral Infection Provide Cross-Protection Against Subsequent Respiratory Viral Infections? A Systematic Review and Meta-Analysis.

The epidemiology of different respiratory viral infections is believed to be affected by prior viral infections in addition to seasonal effects. This PROSPERO-registered systematic review identified 7388 studies, of which six met our criteria to answer the question specifically. The purpose of this review was to compare the prevalence of sequential viral infections in those with previously documented positive versus negative swabs. The pooled prevalence of sequential viral infections over varying periods from 30-1000 days of follow-up was higher following a negative respiratory viral swab at 0.15 than following a positive swab at 0.08, indicating the potential protective effects of prior respiratory viral infections. However, significant heterogeneity and publication biases were noted. There is some evidence, albeit of low quality, of a possible protective effect of an initial viral infection against subsequent infections by a different virus, which is possibly due to broad, nonspecific innate immunity. Future prospective studies are needed to validate our findings.

Graphene-based materials as nanoplatforms for antiviral therapy and prophylaxis.

INTRODUCTION: The dramatic effects caused by viral diseases have prompted the search for effective therapeutic and preventive agents. In this context, 2D graphene-based nanomaterials (GBNs) have shown great potential for antiviral therapy, enabling the functionalization and/or decoration with biomolecules, metals and polymers, able to improve their interaction with viral nanoparticles. AREAS COVERED: This review summarizes the most recent advances of the antiviral research related to 2D GBNs, based on their antiviral mechanism of action. Their ability to inactivate viruses by inhibiting the entry inside cells, or through drug/gene delivery, or by stimulating the host immune response are here discussed. As reported, biological studies performed in vitro and/or in vivo allowed to demonstrate the antiviral activity of the developed GBNs, at different stages of the virus life cycle and the evaluation of their long-term toxicity. Other mechanisms closely related to the physicochemical properties of GBNs are also reported, demonstrating the potential of these materials for antiviral prophylaxis. EXPERT OPINION: GBNs represent valuable tools to fight emerging or reemerging viral infections. However, their translation into the clinic requires standardized scale-up procedures leading to the reliable and reproducible synthesis of these nanomaterials with suitable physicochemical properties, as well as more in-depth pharmacological and toxicological investigations. We believe that multidisciplinary approaches will give valuable solutions to overcome the encountered limitations in the application of GBNs in biomedical and clinical field.

HEX17(Neumifil): An intranasal respiratory biotherapeutic with broad-acting antiviral activity.

Broad-acting antiviral strategies to prevent respiratory tract infections are urgently required. Emerging or re-emerging viral diseases caused by new or genetic variants of viruses such as influenza viruses (IFVs), respiratory syncytial viruses (RSVs), human rhinoviruses (HRVs), parainfluenza viruses (PIVs) or coronaviruses (CoVs), pose a severe threat to human health, particularly in the very young or old, or in those with pre-existing respiratory conditions such as asthma or chronic obstructive pulmonary disease (COPD). Although vaccines remain a key component in controlling and preventing viral infections, they are unable to provide broad-spectrum protection against recurring seasonal infections or newly emerging threats. HEX17 (aka Neumifil), is a first-in-class protein-based antiviral prophylactic for respiratory viral infections. HEX17 consists of a hexavalent carbohydrate-binding module (CBM) with high affinity to sialic acids, which are typically present on terminating branches of glycans on viral cellular receptors. This allows HEX17 to block virus engagement of host receptors and inhibit infection of a wide range of viral pathogens and their variants with reduced risk of antiviral resistance. As described herein, HEX17 has demonstrated broad-spectrum efficacy against respiratory viral pathogens including IFV, RSV, CoV and HRV in multiple in vivo and in vitro studies. In addition, HEX17 can be easily administered via an intranasal spray and is currently undergoing clinical trials.

The significance of stem cell-like memory T cells in viral and bacterial vaccines: A mini review.

Vaccination has become a widely used method to induce immune protection against microbial pathogens, including viral and bacterial microorganisms. Both humoral and cellular immunity serve a critical role in neutralizing and eliminating these pathogens. An effective vaccine should be able to induce a long-lasting immune memory response. Recent investigations on different subsets of T cells have identified a new subset of T cells using multi-parameter flow cytometry, which possess stem cell-like properties and the ability to mount a rapid immune response upon re-exposure to antigens known as stem cell-like memory T cells (TSCM). One of the major challenges with current vaccines is their limited ability to maintain long-term memory in the adaptive immune system. Recent evidence suggests that a specific subgroup of memory T cells has the unique ability to retain their longevity for up to 25 years, as observed in the case of the yellow fever vaccine. Therefore, in this study, we tried to explore and discuss the potential role of this new T cell memory subset in the development of viral and bacterial vaccines.

A Comprehensive Review of Our Understanding and Challenges of Viral Vaccines against Swine Pathogens.

Pig farming has become a strategically significant and economically important industry across the globe. It is also a potentially vulnerable sector due to challenges posed by transboundary diseases in which viral infections are at the forefront. Among the porcine viral diseases, African swine fever, classical swine fever, foot and mouth disease, porcine reproductive and respiratory syndrome, pseudorabies, swine influenza, and transmissible gastroenteritis are some of the diseases that cause substantial economic losses in the pig industry. It is a well-established fact that vaccination is undoubtedly the most effective strategy to control viral infections in animals. From the period of Jenner and Pasteur to the recent new-generation technology era, the development of vaccines has contributed significantly to reducing the burden of viral infections on animals and humans. Inactivated and modified live viral vaccines provide partial protection against key pathogens. However, there is a need to improve these vaccines to address emerging infections more comprehensively and ensure their safety. The recent reports on new-generation vaccines against swine viruses like DNA, viral-vector-based replicon, chimeric, peptide, plant-made, virus-like particle, and nanoparticle-based vaccines are very encouraging. The current review gathers comprehensive information on the available vaccines and the future perspectives on porcine viral vaccines.

mRNA vaccines against infectious diseases and future direction.

Vaccines are used for the control of infectious diseases of animals. Over other types of vaccinations like live attenuated or killed vaccines, mRNA-based vaccines have significant advantages. As only a small portion of the pathogen's genetic material is employed and the dose rate of mRNA-based vaccines is low, there is the least possibility that the pathogen will reverse itself. A carrier or vehicle that shields mRNA-based vaccines from the host's cellular RNases is necessary for their delivery. mRNA vaccines have been shown to be effective and to induce both a cell-mediated immune response and a humoral immune response in clinical trials against various infectious diseases (viral and parasitic) affecting the animals, including rabies, foot and mouth disease, toxoplasmosis, Zikavirus, leishmaniasis, and COVID-19. The current review aims to highlight the use of mRNA-based vaccines both in viral and parasitic diseases of animals.

Epidemiology and Management of Infections in Liver Transplant Recipients.

Background: Improvements in liver transplant (LT) outcomes are attributed to advances in surgical techniques, use of potent immunosuppressants, and rigorous pre-LT testing. Despite these improvements, post-LT infections remain the most common complication in this population. Bacteria constitute the most common infectious agents, while fungal and viral infections are also frequently encountered. Multi-drug-resistant bacterial infections develop because of polymicrobial overuse and prolonged hospital stays. Immediate post-LT infections are commonly caused by viruses. Conclusions: Appropriate vaccination, screening of both donor and recipients before LT and antiviral prophylaxis in high-risk individuals are recommended. Antimicrobial drug resistance is common in high-risk LT and associated with poor outcomes; epidemiology and management of these cases is discussed. Additionally, we also discuss the effect of coronavirus disease 2019 (COVID-19) infection and monkeypox in the LT population.

The use of proteins and peptides-based therapy in managing and preventing pathogenic viruses.

Therapeutic proteins have been employed for centuries and reached approximately 50 % of all drugs investigated. By 2023, they represented one of the top 10 largest-selling pharma products ($387.03 billion) and are anticipated to reach around $653.35 billion by 2030. Growth hormones, insulin, and interferon (IFN α, γ, and ß) are among the leading applied therapeutic proteins with a higher market share. Protein-based therapies have opened new opportunities to control various diseases, including metabolic disorders, tumors, and viral outbreaks. Advanced recombinant DNA biotechnology has offered the production of therapeutic proteins and peptides for vaccination, drugs, and diagnostic tools. Prokaryotic and eukaryotic expression host systems, including bacterial, fungal, animal, mammalian, and plant cells usually applied for recombinant therapeutic proteins large-scale production. However, several limitations face therapeutic protein production and applications at the commercial level, including immunogenicity, integrity concerns, protein stability, and protein degradation under different circumstances. In this regard, protein-engineering strategies such as PEGylation, glycol-engineering, Fc-fusion, albumin conjugation, and fusion, assist in increasing targeting, product purity, production yield, functionality, and the half-life of therapeutic protein circulation. Therefore, a comprehensive insight into therapeutic protein research and findings pave the way for their successful implementation, which will be discussed in the current review.

Coletânea de Respostas Rápidas-Turma 1: programa educacional em vigilância em saúde no enfrentamento da COVID-19 e de outras doenças virais VigiEpidemia / Collection of Rapid Responses-Class 1: educational program in health surveillance in coping with COVID-19 and other viral diseases VigiEpidemia

Coletânea dedicada aos estudos das respostas rápidas do Programa Educacional em Vigilância em Saúde no enfrentamento da COVID-19 e outras Doenças Virais (VigiEpidemia). Esse tema é de extrema relevância e atualidade em nosso contexto da saúde global e na resposta as emergências em saúde pública (ESP) de forma geral. As ESP, que englobam surtos e epidemias, desastres e desassistência à população, representam desafios complexos que exigem respostas ágeis e eficazes por parte das autoridades sanitárias, profissionais da saúde e comunidades como um todo. Até o momento, a pandemia de COVID-19 foi a maior ESP do Século XXI. Ela serviu como um lembrete doloroso da vulnerabilidade da humanidade diante da ameaça de doenças virais. Esta ESP, que teve resposta catastrófica em diversos momentos, evidenciou a importância do investimento em preparação, vigilância e resposta, destacando a necessidade de sistemas de vigilância robustos, colaboração internacional, Inteligência epidemiológica e comunicação transparente para mitigar o impacto devastador das doenças infecciosas na sociedade. As lições aprendidas com a pandemia de COVID-19 são vastas e multifacetadas. A importância da pesquisa, da educação em saúde e do desenvolvimento de vacinas foi evidenciada como uma prioridade crucial na proteção da saúde pública mundial. O investimento em pesquisas e em cursos para formação de profissionais que possam estar atentos as mudanças nos padrões e comportamentos das doenças infecciosas, além de atuar na resposta rápida quando necessário, é fundamental para estarmos preparados para as futuras pandemias. A vacinação, por exemplo, sempre foi uma das ferramentas mais poderosas para evitar surtos e epidemias e, durante a pandemia de COVID-19, ajudou a controlar os óbitos pela doença e possibilitou que voltássemos a ter uma vida normal. Além da vacina contra COVID-19, as vacinas de influenza e dengue também são exemplos notáveis de avanços científicos que desempenham um papel fundamental na prevenção de futuras ESP. Ao explorar os diversos aspectos da resposta, monitoramento e controle de surtos, epidemias e pandemias, esta coletânea visa fornecer uma compreensão abrangente dos desafios enfrentados, das melhores práticas e das estratégias eficazes para mitigar os impactos adversos desses eventos. Espera-se que este trabalho não apenas informe e eduque, mas também inspire ações concretas para fortalecer a recuperação e resiliência dos sistemas de saúde e proteger o bem-estar das comunidades mais vulneráveis do nosso pais.

A collection dedicated to the study of rapid responses by the Educational Program in Health Surveillance in addressing COVID-19 and other Viral Diseases (VigiEpidemia). This theme is of utmost relevance and timeliness in our context of global health and in responding to public health emergencies (PHE) in general. PHEs, which encompass outbreaks and epidemics, disasters, and neglect of the population, represent complex challenges that require swift and effective responses from health authorities, healthcare professionals, and communities as a whole. To date, the COVID-19 pandemic has been the largest PHE of the 21st century. It served as a painful reminder of humanity's vulnerability in the face of viral disease threats. This PHE, which had catastrophic responses at various times, highlighted the importance of investing in preparedness, surveillance, and response, underscoring the need for robust surveillance systems, international collaboration, epidemiological intelligence, and transparent communication to mitigate the devastating impact of infectious diseases on society. The lessons learned from the COVID-19 pandemic are vast and multifaceted. The importance of research, health education, and vaccine development was highlighted as a crucial priority in protecting global public health. Investing in research and training courses to prepare professionals who can be attentive to changes in the patterns and behaviors of infectious diseases and act quickly when needed is essential to be prepared for future pandemics. Vaccination, for example, has always been one of the most powerful tools to prevent outbreaks and epidemics, and during the COVID-19 pandemic, it helped control disease-related deaths and allowed us to return to a normal life. In addition to the COVID-19 vaccine, influenza and dengue vaccines are also notable examples of scientific advancements that play a key role in preventing future PHEs. By exploring the various aspects of response, monitoring, and control of outbreaks, epidemics, and pandemics, this collection aims to provide a comprehensive understanding of the challenges faced, best practices, and effective strategies to mitigate the adverse impacts of these events. It is hoped that this work will not only inform and educate but also inspire concrete actions to strengthen the recovery and resilience of health systems and protect the well-being of the most vulnerable communities in our country.

Gut microbial features may influence antiviral IgG levels after vaccination against viral respiratory infectious diseases: the evidence from two-sample bidirectional mendelian randomization.

BACKGROUND: Vaccination is effective in preventing viral respiratory infectious diseases through protective antibodies and the gut microbiome has been proven to regulate human immunity. This study explores the causal correlations between gut microbial features and serum-specific antiviral immunoglobulin G (IgG) levels. METHODS: We conduct a two-sample bidirectional Mendelian randomization (MR) analysis using genome-wide association study (GWAS) summary data to explore the causal relationships between 412 gut microbial features and four antiviral IgG (for influenza A, measles, rubella, and mumps) levels. To make the results more reliable, we used four robust methods and performed comprehensive sensitivity analyses. RESULTS: The MR analyses revealed 26, 13, 20, and 18 causal associations of the gut microbial features influencing four IgG levels separately. ​Interestingly, ten microbial features, like genus Collinsella, species Bifidobacterium longum, and the biosynthesis of L-alanine have shown the capacity to regulate multiple IgG levels with consistent direction (rise or fall). The ​reverse MR analysis suggested several potential causal associations of IgG levels affecting microbial features. CONCLUSIONS: The human immune response against viral respiratory infectious diseases could be modulated by changing the abundance of gut microbes, which provided new approaches for the intervention of viral respiratory infections.

Haemodialysis machine designation for patients with chronic Hepatitis B virus: A practice and attitudes survey of Australian renal healthcare workers.

BACKGROUND: To reduce the risk of viral transmission, guidelines recommend the use of designated haemodialysis machines and patient isolation for patients with chronic hepatitis B virus (HBV). These practices are without a strong evidence base, and may no longer be necessary in the setting of heat disinfection programs and standard precautions. METHODS: An online cross-sectional survey was developed for renal clinicians across Australia and New Zealand to explore infection prevention policy concerning patients with chronic HBV in haemodialysis units. We sought to determine whether psychosocial and cultural impacts might result from the mandatory use of machine designation and patient isolation practices, as perceived by multidisciplinary healthcare workers with experience working with this patient population. RESULTS: Sixty-seven responses from 27 health districts across all states of Australia and one New Zealand district were received. Most respondents were from urban areas (65%), and were nurses (87%). 50% of health districts reported using designated machines, while 32% isolate patients. Lack of necessary resources limited the use of designated machines (57%), and patient isolation (78%). Respondents not routinely using these precautions were more likely to express concerns regarding patient psychosocial wellbeing and cultural appropriateness. Overall, 30% of respondents expressed concerns regarding the cultural appropriateness of these recommendations. CONCLUSION: We demonstrate wide variation in haemodialysis infection prevention and control policy and practice with regards to managing patients with chronic HBV. While use of standard precautions and machine disinfection are consistently applied, resource availability and concerns for patient psychosocial wellbeing limit adherence to international guidelines.

Harnessing CRISPR technology for viral therapeutics and vaccines: from preclinical studies to clinical applications.

The CRISPR/Cas system, identified as a type of bacterial adaptive immune system, have attracted significant attention due to its remarkable ability to precisely detect and eliminate foreign genetic material and nucleic acids. Expanding upon these inherent capabilities, recent investigations have unveiled the potential of reprogrammed CRISPR/Cas 9, 12, and 13 systems for treating viral infections associated with human diseases, specifically targeting DNA and RNA viruses, respectively. Of particular interest is the RNA virus responsible for the recent global outbreak of coronavirus disease 2019 (COVID-19), which presents a substantial public health risk, coupled with limited efficacy of current prophylactic and therapeutic techniques. In this regard, the utilization of CRISPR/Cas technology offers a promising gene editing approach to overcome the limitations of conventional methods in managing viral infections. This comprehensive review provides an overview of the latest CRISPR/Cas-based therapeutic and vaccine strategies employed to combat human viral infections. Additionally, we discuss significant challenges and offer insights into the future prospects of this cutting-edge gene editing technology.

Respiratory viral infections during Hajj seasons.

Respiratory viral infections pose a public health concern during mass gathering (MG) events. Sustainable and continuous surveillance of respiratory viruses remains a priority to early identify and prevent potential outbreaks. This article reviews recent literature addressed the prevalence and diversity of circulating respiratory viruses during Hajj pilgrimage, one of the largest planned religious MG events held annually in Saudi Arabia. The variation between studies with respect to study design, sample size, time of sample collection (pre-, during, and pos-Hajj), type of participants (e.g., symptomatic vs. a symptomatic pilgrims), and laboratory procedure was highlighted. The majority of these studies were conducted on the 2019 Hajj season or earlier, prior to the emergence of COVID-19 which had significant impact on the past three Hajj seasons (2020, 2021, and 2022). A summary about key aspects related to organization of Hajj during COVID-19 pandemic and the implementation of exceptional infection control strategies is provided.

Healthcare-associated respiratory viral infections after discontinuing universal masking.

In November 2022, our pediatric hospital replaced the requirement for universal masking of all healthcare personnel and visitors in all clinical buildings with a requirement for masking only during patient encounters. Following this change, we observed an immediate, substantial, and sustained increase in healthcare-associated respiratory viral infections.

Analysing the interplay of environmental virology, public health, and sanitation: a comprehensive review from a Kenyan perspective.

This comprehensive review examines the interplay between environmental virology, public health, and sanitation in the unique context of Kenya. The review sheds light on the specific viral threats faced by the country, including waterborne viruses, zoonotic infections, and emerging viral diseases, and their implications for public health. It explores the prevailing public health challenges in Kenya associated with environmental viromics, such as infectious viral diseases, and the rising burden of other infectious particles. The role of sanitation in mitigating viral infections is highlighted, emphasising the importance of clean water supply, proper waste management, and hygienic practises. The review also presents strategies for strengthening environmental virology research in Kenya, including enhancing laboratory capacities and leveraging technological advancements. Furthermore, the policy implications and recommendations derived from the review emphasise the need for multi-sectoral collaboration, evidence-based decision-making, and long-term investments in infrastructure and behaviour change interventions. Implementing these strategies can enhance the understanding of environmental virology, improve public health outcomes, and ensure sustainable sanitation practises in Kenya, ultimately contributing to the well-being of the population and sustainable development.