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A New Generation of Vaccines in the Age of Immunotherapy.

Purpose of reviewCancer vaccines are one of the most extensively studied immunotherapy type in solid tumors. Despite favorable presuppositions, so far, the use of cancer vaccines has been associated with disappointing results. However, a new generation of vaccines has been developed, promising to revolutionize the immunotherapy field.Recent findingsIn this review, we aim to highlight the advances in cancer vaccines and the remaining hurdles to overcome. Cancer vaccination has experienced tremendous progress in the last decade, with myriad promising developments. Future efforts should focus on

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… This approach is being challenged by the use of RNA replicons [ 58 ]. As the latter are self-replicating, they are thought to be longer lasting than mRNA vaccines and may require fewer vaccinations to elicit the desired response. … Replicon RNA viral vectors as vaccines. Vaccines (Basel). 2016;4. 10.3390/vaccines4040039 PMC5192359 27827980 59. …

mRNA vaccine in cancer therapy: Current advance and future outlook.

Messenger ribonucleic acid (mRNA) vaccines are a relatively new class of vaccines that have shown great promise in the immunotherapy of a wide variety of infectious diseases and cancer. In the past 2 years, SARS-CoV-2 mRNA vaccines have contributed tremendously against SARS-CoV2, which has prompted the arrival of the mRNA vaccine research boom, especially in the research of cancer vaccines. Compared with conventional cancer vaccines, mRNA vaccines have significant advantages, including efficient production of protective immune responses, relatively low side effects and lower cost of acquisitio

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… Self‐amplifying replicon RNA vaccine delivery to dendritic cells by synthetic nanoparticles . Vaccines . 2014 ; 2 ( 4 ): 735 ‐ 754 . 26344889 10.3390/vaccines2040735 PMC4494254 86 Xu J , Luft JC , Yi X , et al. RNA replicon delivery via lipid‐complexed PRINT protein particles . … Replicon RNA viral vectors as vaccines . Vaccines . 2016 ; 4 ( 4 ): 39 . doi: 10.3390/vaccines4040039 27827980 PMC5192359 101 Beissert T , Perkovic M , Vogel A , et al. A trans‐amplifying RNA vaccine strategy for induction of potent protective immunity . …

Characterization of the prevalence of Salmonella in different retail chicken supply modes using genome-wide and machine-learning analyses.

Salmonella is a foodborne pathogen that causes salmonellosis, of which retail chicken meat is a major source. However, the prevalence of Sal … rozen mode isolates on a complex transposon consisting of TnAS3-IS26. Virulence factors and plasmid replicons were abundant in the studied frozen mode isolates. In addition, single nucleotide polymorphism (SNP) phylogenetic tree results showed that in the frozen supply mode, the S. Enteritidis clonal clade continued to contaminate retail chicken meat and w …

Whole-Genome Sequencing Uncovers Chromosomal and Plasmid-Borne Multidrug Resistance and Virulence Genes in Poultry-Associated Escherichia coli from Nigeria.

BACKGROUND: Broad and unregulated antibiotic use in livestock production, particularly poultry farming, has increased the development and pe … ombining Illumina and Nanopore platforms, followed by genome assembly and annotation. ARGs, plasmid replicons, and virulence factors were identified in silico using AMRFinderPlus, starAMR, RGI/CARD, PlasmidFinder, MOB-suite, and the Virulence Factor Database (VFDB). RESULTS: Phenotypic testing revealed extensive resistance, with complete resistance to six …

Clinical and Genomic Epidemiology of Carbapenem-Nonsusceptible Citrobacter spp. at a Tertiary Health Care Center over 2 Decades.

Carbapenem-nonsusceptible Citrobacter spp. (CNSC) are increasingly recognized as health care-associated pathogens. Information regarding their clinical epidemiology, genetic diversity, and mechanisms of carbapenem resistance is lacking. We examined microbiology records of adult patients at the University of Pittsburgh Medical Center (UMPC) Presbyterian Hospital (PUH) from 2000 to 2018 for CNSC, as defined by ertapenem nonsusceptibility. Over this time frame, the proportion of CNSC increased from 4% to 10% (P = 0.03), as did daily defined carbapenem doses/1,000 patient days (6.52 to 34.5; R2 =

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… A total of 11 complete, circular contigs were resolved from 10 isolates and nine patients, and all but one of these contigs contained replicons belonging to the IncA/C2, IncL/M, IncN, and unnamed RepA families. … Additionally, the YDC876 genome contained two plasmids of different sizes with distinct replicons that both harbored bla KPC-3 carbapenemase genes. …

Molecular characteristics and antimicrobial susceptibility of carbapenem-resistant Klebsiella pneumoniae in a multicenter study in Ningbo, China.

OBJECTIVE: To analyze the molecular epidemiology and antimicrobial resistance profiles of carbapenem-resistant Klebsiella pneumoniae (CR-KP) … nder online tool (https://cge.food.dtu.dk/services/PlasmidFinder/) was utilized to identify plasmid replicon genes and perform Inc. typing analysis. Furthermore, to conduct a comprehensive collinearity analysis of the bla KPC-2 resistance plasmid gene, gene cluster maps were constructed using Bakta v1.11.0 and Clinker v0.0.28 software packages. RESULTS: A …

Genome-Based Assessment of Antimicrobial Resistance and Virulence Potential of Isolates of Non-Pullorum/Gallinarum Salmonella Serovars Recovered from Dead Poultry in China.

Paratyphoid avian salmonellosis is considered one of the leading causes of poultry death, resulting in significant economic losses to poultr … d DNA topoisomerase IV (parC) genes, conferring resistance to quinolones. The prediction of plasmid replicons detected 14 types, with a dominance of IncFIB(S)_1 and IncFII(S)_1 (87.62% for both), while the IncX1 plasmid type was considered the key carrier of antimicrobial resistance determinants. Moreover, we report the detection of critical virulence gene …

Xanthohumol: Mechanistic Actions and Emerging Evidence as a Multi-Target Natural Nutraceutical.

BACKGROUND: Xanthohumol (XN), a prenylated chalcone flavonoid derived from hops (Humulus lupulus), is increasingly recognized as a highly pleiotropic natural compound. OBJECTIVE: We aimed to structure XN's mechanistic hierarchy with emerging translational relevance across disease areas. METHODS: We performed a comprehensive and integrative literature review of XN for its biological and translational effects across cancer, metabolic, neurological, cardiovascular, hepatic, renal, and dermatological disorders. RESULTS: Mechanistically, XN exerts diverse bioactivities by inhibiting major pro-on

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… Anti-HCV: XN demonstrated dose-dependent activity of anti-HCV replicons [ 46 ]. At concentrations of 7.05–14.11 μM, XN achieved inhibitory effects comparable to interferon-alpha 2b, producing similar reductions in HCV RNA levels [ 46 ]. … Relative to antiviral standards, XN achieved inhibitory effects comparable to interferon-α2b in HCV replicon systems and displayed greater potency than ribavirin but less than interferon-α in the BVDV surrogate model [ 46 , 47 ]. Synergy with interferon-α has also been observed against HCV. …

Convergence and global molecular epidemiology of Klebsiella pneumoniae plasmids harbouring the iuc3 virulence locus: a population genomic analysis.

BACKGROUND: Klebsiella pneumoniae is an important pathogen of humans and animals. In the past five years, increasing reports of convergent s … nged in size from 110 375 bp to 365 580 bp and mostly corresponded to multiple IncFIB(K) and IncFII replicon types. We found seven convergent K pneumoniae plasmids in the Thai data: six from fresh markets and one from a neighbouring hospital. These plasmids emerged through the hybridisation of cocirculating iuc3 plasmids and plasmids encoding extended-spec …

Genome Editing Approaches with CRISPR/Cas9 for Cancer Treatment: Critical Appraisal of Preclinical and Clinical Utility, Challenges, and Future Research.

The increasing burden on human malignant diseases became a major concern for healthcare practitioners, that must deal with tumor relapse and the inability to efficiently treat metastasis, in addition to side effects. Throughout the decades, many therapeutic strategies have been employed to improve the clinical outcomes of cancer patients and great efforts have been made to develop more efficient and targeted medicines. The malignant cell is characterized by genetic and epigenetic modifications, therefore targeting those specific drivers of carcinogenesis is highly desirable. Among the genome e

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… Long Stretches of Short Tandem Repeats Are Present in the Largest Replicons of the Archaea Haloferax Mediterranei and Haloferax Volcanii and Could Be Involved in Replicon Partitioning. Mol. Microbiol. 1995;17:85–93. doi: 10.1111/j.1365-2958.1995.mmi_17010085.x. 18. …

mRNA vaccine development and applications: A special focus on tumors (Review).

Cancer is characterized by unlimited proliferation and metastasis, and traditional therapeutic strategies usually result in the acquisition of drug resistance, thus highlighting the need for more personalized treatment. mRNA vaccines transfer the gene sequences of exogenous target antigens into human cells through transcription and translation to stimulate the body to produce specific immune responses against the encoded proteins, so as to enable the body to obtain immune protection against said antigens; this approach may be adopted for personalized cancer therapy. Since the recent coronaviru

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… Self-amplifying or replicon RNA vaccines and non-replicating mRNA vaccines are the two primary types of RNA vaccines that have been assessed. … Replicons are self-amplifying mRNAs that are produced from RNA viruses that have had their structural viral proteins replaced with mRNA-encoding RNA polymerases and antigens. Thus, these mRNAs enhance immunogenicity and extend protein expression, thereby improving efficiency ( 104 , 105 ). …

Predominance of Non-carbapenemase Producing Carbapenem-Resistant Enterobacterales in South Texas.

BackgroundCarbapenem-resistant Enterobacterales (CRE) pose a significant global public health threat. Resistance among CRE is particularly complex, owing to numerous possible resistance mechanisms and broad definitions. We aimed to characterize the clinical and molecular profiles of CRE in the South Texas region.Materials and methodsWe compared the clinical, genotypic, and phenotypic profiles of carbapenemase producing Enterobacterales (CPE) with those of non-carbapenemase producers (NCPE) isolated from South Texas, United States between 2011 and 2019. Molecular characteristics and resistance

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… Both isolates were K. pneumoniae ST307 [replicons IncFII(K)]. Another potential cluster of NCPE among three unique patients admitted on the same hospital floor was identified among K. pneumoniae ST307 (K2312011, K2542011, and K2342012). …

Redefining the battle against colorectal cancer: a comprehensive review of emerging immunotherapies and their clinical efficacy.

Colorectal cancer (CRC) is the third most common cancer globally and presents a significant challenge owing to its high mortality rate and the limitations of traditional treatment options such as surgery, radiotherapy, and chemotherapy. While these treatments are foundational, they are often poorly effective owing to tumor resistance. Immunotherapy is a groundbreaking alternative that has recently emerged and offers new hope for success by exploiting the body's own immune system. This article aims to provide an extensive review of clinical trials evaluating the efficacy of various immunotherap

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… AVX701 is an alphavirus-based viral replicon particle vaccine expressing a modified version of CEA [CEA(6D)] with possible antineoplastic activity. … In the two clinical trials, an alphaviral replicon particle encoding the CEA protein using a self-amplifying mRNA was used. …

Revolutionizing cancer care strategies: immunotherapy, gene therapy, and molecular targeted therapy.

Despite the availability of technological advances in traditional anti-cancer therapies, there is a need for more precise and targeted cancer treatment strategies. The wide-ranging shortfalls of conventional anticancer therapies such as systematic toxicity, compromised life quality, and limited to severe side effects are major areas of concern of conventional cancer treatment approaches. Owing to the expansion of knowledge and technological advancements in the field of cancer biology, more innovative and safe anti-cancerous approaches such as immune therapy, gene therapy and targeted therapy a

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… A study utilizing an alpha-virus plasmid carrying the CEA antigen gene enveloped in virus-like replicon particles (VRP) claimed a reduction in the neutralization effect caused by antibodies and Treg cells, leading to an improvement in immunotherapeutic treatment and overall survival rate [ 43 ]. …

Potential Molecular Targeted Therapy for Unresectable Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers, representing a serious worldwide health concern. The recurrence incidence of hepatocellular carcinoma (HCC) following surgery or ablation is as high as 70%. Thus, the clinical applicability of standard surgery and other locoregional therapy to improve the outcomes of advanced HCC is restricted and far from ideal. The registered trials did not identify a treatment that prolonged recurrence-free survival, the primary outcome of the majority of research. Several investigator-initiated trials have demonstrated that var

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… In a Huh7-based subgenomic replicon, SOF effectively reduced HCV replication, as predicted. By using MTT and Ala blue tests, SOF therapy for 48 or 72 h had no discernible impact on the development of the majority of HCC cells. …

Микроаэробный маленький белок от теплового шока способствует ризобию лимуминозараму/Писуму симбиозу и взаимодействует с широким диапазоном бактерироидных белков.

Во время создания симбиоза с бобовыми растениями ризобия подвергается воздействию враждебной физической и химической микроокружающей среды, к которой требуется адаптация. Протеины реакции на стресс, включая небольшие белки от теплового удара (SHSP), ранее, как было установлено, дифференцировались в бактерироидах, индуцируемых ризобием лимуминозарум бv. viciae UPM791 в различных хост-узлах. В ходе этой работы мы провели функциональный анализ зависящих от принимающей стороны SHSP RLV_1399. Рlv_1399- Исключенный штамм мутантов был нарушен в симбиотических свойствах гороха, но не чечевиц. Выражени

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… Analysis of the relative mRNA levels of Rlv UPM791 fnrN1 and fnrN2 genes revealed that these genes are expressed at different levels in the bacteroid, probably due to their location at different replicons as previously stated ( 21 , 28 , 29 ). …

Immunomodulatory Nanosystems.

Immunotherapy has emerged as an effective strategy for the prevention and treatment of a variety of diseases, including cancer, infectious diseases, inflammatory diseases, and autoimmune diseases. Immunomodulatory nanosystems can readily improve the therapeutic effects and simultaneously overcome many obstacles facing the treatment method, such as inadequate immune stimulation, off-target side effects, and bioactivity loss of immune agents during circulation. In recent years, researchers have continuously developed nanomaterials with new structures, properties, and functions. This Review provi

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… membrane‐coated PLGA NP | Virulence factors from hSP | – | 261 | Au NP coated with OMV from bacteria | – | 262 Vaccine for other infectious diseases | Plasmonic Au NP | DNA plasmid of hepatitis C virus | – | 244 | PLGA–PLL/γPGA NP | Ebola DNA vaccine | – | 21 | MDNP consisting of dendrimer and lipid‐PEG | Replicon … It was reported that replicon mRNA could achieve sustained translation and amplification of encoded protein. …

Therapeutic Vaccines for Hematological Cancers: A Scoping Review of This Immunotherapeutic Approach as Alternative to the Treatment of These Malignancies.

Background/Objectives: The need for innovative cancer treatments has brought immunotherapies to the forefront as a promising approach, with therapeutic vaccines demonstrating the potential to mobilize immune cells to eliminate tumor cells. However, challenges such as genetic variability among patients, immune evasion mechanisms, and disease relapse contribute to the complexity of achieving an ideal therapy, especially for hematological cancers. This review systematically identifies and analyzes recent studies focused on the development of therapeutic immunotherapy vaccines, examining critical

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… Alphavirus Replicon Particle Vaccine Breaks B Cell Tolerance and Rapidly Induces IgG to Murine Hematolymphoid Tumor Associated Antigens Front. Immunol. 2022 13 865486 10.3389/fimmu.2022.865486 35686131 PMC9171395 68. Du Z. Huang Z. Chen X. Jiang G. Peng Y. Feng W. Huang N. …

Control of viral infections by epigenetic-targeted therapy.

Epigenetics is defined as the science that studies the modifications of gene expression that are not owed to mutations or changes in the genetic sequence. Recently, strong evidences are pinpointing toward a solid interplay between such epigenetic alterations and the outcome of human cytomegalovirus (HCMV) infection. Guided by the previous possibly promising experimental trials of human immunodeficiency virus (HIV) epigenetic reprogramming, the latter is paving the road toward two major approaches to control viral gene expression or latency. Reactivating HCMV from the latent phase ("shock and k

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… Selective inhibitor of histone deacetylase 6 (tubastatin A) suppresses proliferation of hepatitis C virus replicon in culture of human hepatocytes. Biochemistry (Mosc) 2014;79:637–642. doi: 10.1134/S0006297914070050. 138. Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, et al. …

A review on Gaucher disease: therapeutic potential of β-glucocerebrosidase-targeted mRNA/saRNA approach.

Gaucher disease (GD), a rare hereditary lysosomal storage disorder, occurs due to a deficiency in the enzyme β-glucocerebrosidase (GCase). This deficiency leads to the buildup of substrate glucosylceramide (GlcCer) in macrophages, eventually resulting in various complications. Among its three types, GD2 is particularly severe with neurological involvements. Current treatments, such as enzyme replacement therapy (ERT), are not effective for GD2 and GD3 due to their inability to cross the blood-brain barrier (BBB). Other treatment approaches, such as gene or chaperone therapies are still in expe