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Emerging Microbes & Infections Dec 2023African swine fever (ASF) is an acute and highly contagious lethal infectious disease in swine that severely threatens the global pig industry. At present, a safe and...
African swine fever (ASF) is an acute and highly contagious lethal infectious disease in swine that severely threatens the global pig industry. At present, a safe and efficacious vaccine is urgently required to prevent and control the disease. In this study, we evaluated the safety and immunogenicity of replication-incompetent type-2 adenoviruses carrying African swine fever virus (ASFV) antigens, namely (p30), (p54), (CD2v), (p72), and (p72 chaperone). A vaccine cocktail delivered by simultaneous intramuscular (IM) and intranasal (IN) administration robustly elicited both systemic and mucosal immune responses against AFSV in mice and swine and provided highly effective protection against the circulating ASFV strain in farmed pigs. This multi-antigen cocktail vaccine was well tolerated in the vaccinated animals. No significant interference among antigens was observed. The combined IM and IN vaccination using this adenovirus-vectored antigen cocktail vaccine warrants further evaluation for providing safe and effective protection against ASFV infection and transmission.
Topics: Swine; Animals; Mice; African Swine Fever Virus; African Swine Fever; Adenoviridae; Adenovirus Vaccines; Antigens, Viral; Viral Vaccines; Adenoviridae Infections; Vaccination
PubMed: 37401832
DOI: 10.1080/22221751.2023.2233643 -
World Journal of Virology Jun 2023Viral gastroenteritis is the most common viral illness that affects the gastrointestinal (GI) tract, causing inflammation and irritation of the lining of the stomach and... (Review)
Review
Viral gastroenteritis is the most common viral illness that affects the gastrointestinal (GI) tract, causing inflammation and irritation of the lining of the stomach and intestines. Common signs and symptoms associated with this condition include abdominal pain, diarrhea, and dehydration. The infections commonly involved in viral gastroenteritis are rotavirus, norovirus, and adenovirus, which spread through the fecal-oral and contact routes and cause non-bloody diarrhea. These infections can affect both immunocompetent and immunocompromised individuals. Since the pandemic in 2019, coronavirus gastroenteritis has increased in incidence and prevalence. Morbidity and mortality rates from viral gastroenteritis have declined significantly over the years due to early recognition, treatment with oral rehydration salts, and prompt vaccination. Improved sanitation measures have also played a key role in reducing the transmission of infection. In addition to viral hepatitis causing liver disease, herpes virus, and cytomegalovirus are responsible for ulcerative GI disease. They are associated with bloody diarrhea and commonly occur in im-munocompromised individuals. Hepatitis viruses, Epstein-Barr virus, herpesvirus 8, and human papillomavirus have been involved in benign and malignant diseases. This mini review aims to list different viruses affecting the GI tract. It will cover common symptoms aiding in diagnosis and various important aspects of each viral infection that can aid diagnosis and management. This will help primary care physicians and hospitalists diagnose and treat patients more easily.
PubMed: 37396706
DOI: 10.5501/wjv.v12.i3.136 -
Molecular Therapy. Nucleic Acids Dec 2023Adenoviral vectors have been widely used as vaccine candidates or potential vaccine candidates against infectious diseases due to the convenience of genome manipulation,... (Review)
Review
Adenoviral vectors have been widely used as vaccine candidates or potential vaccine candidates against infectious diseases due to the convenience of genome manipulation, their ability to accommodate large exogenous gene fragments, easy access of obtaining high-titer of virus, and high efficiency of transduction. At the same time, adenoviral vectors have also been used extensively in clinical research for cancer gene therapy and treatment of diseases caused by a single gene defect. However, application of adenovirus also faces a series of challenges such as poor targeting, strong immune response against the vector itself, and they cannot be used repeatedly. It is believed that these problems will be solved gradually with further research and technological development in related fields. Here, we review the construction methods of adenoviral vectors, including "gutless" adenovirus and discuss application of adenoviral vectors as prophylactic vaccines for infectious pathogens and their application prospects as therapeutic vaccines for cancer and other kinds of chronic infectious disease such as human papillomavirus, hepatitis B virus, and hepatitis C virus.
PubMed: 37808925
DOI: 10.1016/j.omtn.2023.09.004 -
Cancer Letters Nov 2023Pancreatic cancer remains one of the deadliest cancers with extremely high mortality rate, and the number of cases is expected to steadily increase with time. Pancreatic... (Review)
Review
Pancreatic cancer remains one of the deadliest cancers with extremely high mortality rate, and the number of cases is expected to steadily increase with time. Pancreatic cancer is refractory to conventional cancer treatment options, like chemotherapy and radiotherapy, and commercialized immunotherapeutics, owing to its immunosuppressive and desmoplastic phenotype. Due to these reasons, development of an innovative treatment option that can overcome these challenges posed by the pancreatic tumor microenvironment (TME) is in an urgent need. The present review aims to summarize the evolution of oncolytic adenovirus (oAd) engineering and usage as therapeutics (either monotherapy or combination therapy) over the last decade to overcome these hurdles to instigate a potent antitumor effect against desmoplastic and immunosuppressive pancreatic cancer.
Topics: Humans; Oncolytic Virotherapy; Oncolytic Viruses; Adenoviridae; Pancreatic Neoplasms; Cell Line, Tumor; Tumor Microenvironment
PubMed: 37940067
DOI: 10.1016/j.canlet.2023.216456 -
Circulation Research Feb 2024The sympathoadrenergic system and its major effector PKA (protein kinase A) are activated to maintain cardiac output coping with physiological or pathological stressors....
BACKGROUND
The sympathoadrenergic system and its major effector PKA (protein kinase A) are activated to maintain cardiac output coping with physiological or pathological stressors. If and how PKA plays a role in physiological cardiac hypertrophy (PhCH) and pathological CH (PaCH) are not clear.
METHODS
Transgenic mouse models expressing the PKA inhibition domain (PKAi) of PKA inhibition peptide alpha (PKIalpha)-green fluorescence protein (GFP) fusion protein (PKAi-GFP) in a cardiac-specific and inducible manner (cPKAi) were used to determine the roles of PKA in physiological CH during postnatal growth or induced by swimming, and in PaCH induced by transaortic constriction (TAC) or augmented Ca influx. Kinase profiling was used to determine cPKAi specificity. Echocardiography was used to determine cardiac morphology and function. Western blotting and immunostaining were used to measure protein abundance and phosphorylation. Protein synthesis was assessed by puromycin incorporation and protein degradation by measuring protein ubiquitination and proteasome activity. Neonatal rat cardiomyocytes (NRCMs) infected with AdGFP (GFP adenovirus) or AdPKAi-GFP (PKAi-GFP adenovirus) were used to determine the effects and mechanisms of cPKAi on myocyte hypertrophy. rAAV9.PKAi-GFP was used to treat TAC mice.
RESULTS
(1) cPKAi delayed postnatal cardiac growth and blunted exercise-induced PhCH; (2) PKA was activated in hearts after TAC due to activated sympathoadrenergic system, the loss of endogenous PKIα (PKA inhibition peptide α), and the stimulation by noncanonical PKA activators; (3) cPKAi ameliorated PaCH induced by TAC and increased Ca influxes and blunted neonatal rat cardiomyocyte hypertrophy by isoproterenol and phenylephrine; (4) cPKAi prevented TAC-induced protein synthesis by inhibiting mTOR (mammalian target of rapamycin) signaling through reducing Akt (protein kinase B) activity, but enhancing inhibitory GSK-3α (glycogen synthase kinase-3α) and GSK-3β signals; (5) cPKAi reduced protein degradation by the ubiquitin-proteasome system via decreasing RPN6 phosphorylation; (6) cPKAi increased the expression of antihypertrophic atrial natriuretic peptide (ANP); (7) cPKAi ameliorated established PaCH and improved animal survival.
CONCLUSIONS
Cardiomyocyte PKA is a master regulator of PhCH and PaCH through regulating protein synthesis and degradation. cPKAi can be a novel approach to treat PaCH.
Topics: Mice; Rats; Animals; Proteasome Endopeptidase Complex; Cyclic AMP-Dependent Protein Kinases; Glycogen Synthase Kinase 3 beta; Cardiomegaly; Myocytes, Cardiac; Mice, Transgenic; Peptides; Mammals
PubMed: 38275112
DOI: 10.1161/CIRCRESAHA.123.322729 -
Frontiers in Immunology 2023Recurrent glioma treatment is challenging due to molecular heterogeneity and treatment resistance commonly observed in these tumors. Researchers are actively pursuing... (Review)
Review
Recurrent glioma treatment is challenging due to molecular heterogeneity and treatment resistance commonly observed in these tumors. Researchers are actively pursuing new therapeutic strategies. Oncolytic viruses have emerged as a promising option. Oncolytic viruses selectively replicate within tumor cells, destroying them and stimulating the immune system for an enhanced anticancer response. Among Oncolytic viruses investigated for recurrent gliomas, oncolytic herpes simplex virus and oncolytic adenovirus show notable potential. Genetic modifications play a crucial role in optimizing their therapeutic efficacy. Different generations of replicative conditioned oncolytic human adenovirus and oncolytic HSV have been developed, incorporating specific modifications to enhance tumor selectivity, replication efficiency, and immune activation. This review article summarizes these genetic modifications, offering insights into the underlying mechanisms of Oncolytic viruses' therapy. It also aims to identify strategies for further enhancing the therapeutic benefits of Oncolytic viruses. However, it is important to acknowledge that additional research and clinical trials are necessary to establish the safety, efficacy, and optimal utilization of Oncolytic viruses in treating recurrent glioblastoma.
Topics: Humans; Simplexvirus; Adenoviridae; Neoplasm Recurrence, Local; Glioma; Oncolytic Viruses; Adenoviridae Infections
PubMed: 38022620
DOI: 10.3389/fimmu.2023.1285113 -
Vaccines Oct 2023Inducing humoral and cytotoxic mucosal immunity at the sites of pathogen entry has the potential to prevent the infection from getting established. This is different... (Review)
Review
Inducing humoral and cytotoxic mucosal immunity at the sites of pathogen entry has the potential to prevent the infection from getting established. This is different from systemic vaccination, which protects against the development of systemic symptoms. The field of mucosal vaccination has seen fewer technological advances compared to nucleic acid and subunit vaccine advances for injectable vaccine platforms. The advent of the next-generation adenoviral vectors has given a boost to mucosal vaccine research. Basic research into the mechanisms regulating innate and adaptive mucosal immunity and the discovery of effective and safe mucosal vaccine adjuvants will continue to improve mucosal vaccine design. The results from clinical trials of inhaled COVID-19 vaccines demonstrate their ability to induce the proliferation of cytotoxic T cells and the production of secreted IgA and IgG antibodies locally, unlike intramuscular vaccinations. However, these mucosal vaccines induce systemic immune responses at par with systemic vaccinations. This review summarizes the function of the respiratory mucosa-associated lymphoid tissue and the advantages that the adenoviral vectors provide as inhaled vaccine platforms.
PubMed: 37896988
DOI: 10.3390/vaccines11101585 -
International Journal of Public Health 2023This umbrella meta-analysis aims to provide comprehensive and synthesized evidence regarding the effectiveness and safety of COVID-19 vaccinations based on current... (Meta-Analysis)
Meta-Analysis Review
This umbrella meta-analysis aims to provide comprehensive and synthesized evidence regarding the effectiveness and safety of COVID-19 vaccinations based on current studies. Studies from the Cochrane Library, PubMed, and EMBASE, published before 10 December 2021, were included in the analysis. The pooled results of effectiveness and safety were estimated and shown in forest plots. We included nineteen studies (fifteen studies regarding safety and nine regarding effectiveness) in the analysis. The mRNA vaccines, adenovirus vector vaccines, subunit vaccines, and inactivated vaccines were found to be effective; however, mRNA vaccines, adenovirus vector vaccines and subunit vaccines were associated with local adverse events and systemic events when compared with inactivated vaccines. Our study suggested that till date, COVID-19 vaccination is still a preferred pharmaceutical way to control the widespread pandemic. However, all reported adverse events should be revisited to provide further evidence for mass vaccinations.
Topics: Humans; COVID-19 Vaccines; Adenovirus Vaccines; COVID-19; Vaccination; RNA, Messenger
PubMed: 37485047
DOI: 10.3389/ijph.2023.1605526 -
Cell Reports Methods Sep 2023Despite advances in virological sciences and antiviral research, viruses continue to emerge, circulate, and threaten public health. We still lack a comprehensive... (Review)
Review
Despite advances in virological sciences and antiviral research, viruses continue to emerge, circulate, and threaten public health. We still lack a comprehensive understanding of how cells and individuals remain susceptible to infectious agents. This deficiency is in part due to the complexity of viruses, including the cell states controlling virus-host interactions. Microscopy samples distinct cellular infection stages in a multi-parametric, time-resolved manner at molecular resolution and is increasingly enhanced by machine learning and deep learning. Here we discuss how state-of-the-art artificial intelligence (AI) augments light and electron microscopy and advances virological research of cells. We describe current procedures for image denoising, object segmentation, tracking, classification, and super-resolution and showcase examples of how AI has improved the acquisition and analyses of microscopy data. The power of AI-enhanced microscopy will continue to help unravel virus infection mechanisms, develop antiviral agents, and improve viral vectors.
Topics: Humans; Microscopy; Artificial Intelligence; Machine Learning; Antiviral Agents; Viruses
PubMed: 37751685
DOI: 10.1016/j.crmeth.2023.100557