Oncolytic Measles Virotherapy and Opposition to Measles Vaccination

Recent measles epidemics in US and European cities where vaccination coverage has declined are providing a harsh reminder for the need to maintain protective levels of immunity across the entire population. Vaccine uptake rates have been declining in large part because of public misinformation regarding a possible association between measles vaccination and autism for which there is no scientific basis. The purpose of this article is to address a new misinformed antivaccination argument-that measles immunity is undesirable because measles virus is protective against cancer. Having worked for many years to develop engineered measles viruses as anticancer therapies, we have concluded (1) that measles is not protective against cancer and (2) that its potential utility as a cancer therapy will be enhanced, not diminished, by prior vaccination

A phase I oncolytic virus trial with vesicular stomatitis virus expressing human interferon beta and tyrosinase related protein 1 administered intratumorally and intravenously in uveal melanoma: safety, efficacy, and T cell responses

IntroductionMetastatic uveal melanoma (MUM) has a poor prognosis and treatment options are limited. These patients do not typically experience durable responses to immune checkpoint inhibitors (ICIs). Oncolytic viruses (OV) represent a novel approach to immunotherapy for patients with MUM.MethodsWe developed an OV with a Vesicular Stomatitis Virus (VSV) vector modified to express interferon-beta (IFN-β) and Tyrosinase Related Protein 1 (TYRP1) (VSV-IFNβ-TYRP1), and conducted a Phase 1 clinical trial with a 3 + 3 design in patients with MUM. VSV-IFNβ-TYRP1 was injected into a liver metastasis, then administered on the same day as a single intravenous (IV) infusion. The primary objective was safety. Efficacy was a secondary objective.Results12 patients with previously treated MUM were enrolled. Median follow up was 19.1 months. 4 dose levels (DLs) were evaluated. One patient at DL4 experienced dose limiting toxicities (DLTs), including decreased platelet count (grade 3), increased aspartate aminotransferase (AST), and cytokine release syndrome (CRS). 4 patients had stable disease (SD) and 8 patients had progressive disease (PD). Interferon gamma (IFNγ) ELIspot data showed that more patients developed a T cell response to virus encoded TYRP1 at higher DLs, and a subset of patients also had a response to other melanoma antigens, including gp100, suggesting epitope spreading. 3 of the patients who responded to additional melanoma antigens were next treated with ICIs, and 2 of these patients experienced durable responses.DiscussionOur study found that VSV-IFNβ -TYRP1 can be safely administered via intratumoral (IT) and IV routes in a previously treated population of patients with MUM. Although there were no clear objective radiographic responses to VSV-IFNβ-TYRP1, dose-dependent immunogenicity to TYRP1 and other melanoma antigens was seen

Molekularna karakterizacija i računalna analiza gena ompH za glavni protein stanične stijenke bakterije Pasteurella multocida P52.

The major outer membrane protein (OmpH) of P. multocida P52 was identified as one of the major immunodominant antigens. The gene ompH, encoding OmpH, was amplified, cloned and sequenced. The coding region of OmpH is 1,002 bp long. The predicted primary protein is composed of 333 amino acids, with a 20-amino acid signal peptide. The mature protein contains 313 amino acids with a predicted molecular mass of 33,760 Da. The nucleotide sequence and the predicted amino acid sequence of the ompH gene of P. Multocida P52 showed a high level of homology to the OmpH of other serotypes of P. multocida, confirming that the ompH gene is conserved among all the serotypes of P. multocida. Multiple sequence alignment revealed high homology among the serotypes, with major variations confined to two discrete regions (amino acids 82-102 and 223-240), which corresponded to hydrophilic domains showing high antigenicity. The sequence information, presented in this study will open new vistas in progress towards the development of suitable prophylaxis and molecular epidemiological analysis.Glavni protein (OmpH) stanične stijenke bakterije Pasteurella multocida P52 identificiran je kao jedan od glavnih imunodominantnih antigena. Gen ompH što kodira za OmpH bio je umnožen, kloniran i sekvencioniran. Kodirajuće područje za OmpH veličine je 1002 bp. Predviđeni primarni protein sadržava 333 aminokiseline sa signalnim peptidom od 20 aminokiselina. Zreli (konačni) protein sadržava 313 aminokiselina s predviđenom molekularnom masom od 33,760 Da. Nukleotidni slijed i predviđeni aminokiselinski slijed gena ompH bakterije P. multocida P52 pokazao je visoku razinu homolognosti s OmpH drugih serovarova bakterije P. multocida što potvrđuje da je gen ompH konzerviran u svim serovarovima bakterije P. multocida. Višestrukim poravnanjem sljedova dokazana je visoka homolognost među serovarovima s velikom varijabilnošću ograničenom na dva zasebna područja (aminokiseline 82-102 i 223-240), koja odgovaraju hidrofilnim područjima s jakom antigenošću. Rezultati o aminokiselinskom sljedu dobiveni u ovom radu otvorit će nove putove u razvitku prikladne profilakse i molekularne epizootiologije

Distinct Signature of Oxylipid Mediators of Inflammation during Infection and Asymptomatic Colonization by E. coli in the Urinary Bladder

Urinary tract infection (UTI) is an extremely common infectious disease. Uropathogenic Escherichia coli (UPEC) is the predominant etiological agent of UTI. Asymptomatic bacteriuric E. coli (ABEC) strains successfully colonize the urinary tract resulting in asymptomatic bacteriuria (ABU) and do not induce symptoms associated with UTI. Oxylipids are key signaling molecules involved in inflammation. Based on the distinct clinical outcomes of E. coli colonization, we hypothesized that UPEC triggers the production of predominantly proinflammatory oxylipids and ABEC leads to production of primarily anti-inflammatory or proresolving oxylipids in the urinary tract. We performed quantitative detection of 39 oxylipid mediators with proinflammatory, anti-inflammatory, and proresolving properties, during UTI and ABU caused by genetically distinct E. coli strains in the murine urinary bladder. Our results reveal that infection with UPEC causes an increased accumulation of proinflammatory oxylipids as early as 6 h postinoculation, compared to controls. To the contrary, ABEC colonization leads to decreased accumulation of proinflammatory oxylipids at the early time point compared to UPEC infection but does not affect the level of proresolving oxylipids. This report represents the first comprehensive investigation on the oxylipidome during benign ABEC colonization observed in ABU and acute inflammation triggered by UPEC leading to UTI

IoT Based Health—Related Topic Recognition from Emerging Online Health Community (Med Help) Using Machine Learning Technique

The unprompted patient’s and inimitable physician’s experience shared on online health communities (OHCs) contain a wealth of unexploited knowledge. Med Help and eHealth are some of the online health communities offering new insights and solutions to all health issues. Diabetes mellitus (DM), thyroid disorders and tuberculosis (TB) are chronic diseases increasing rapidly every year. As part of the project described in this article comments related to the diseases from Med Help were collected. The comments contain the patient and doctor discussions in an unstructured format. The sematic vision of the internet of things (IoT) plays a vital role in organizing the collected data. We pre-processed the data using standard natural language processing techniques and extracted the essential features of the words using the chi-squared test. After preprocessing the documents, we clustered them using the K-means++ algorithm, which is a popular centroid-based unsupervised iterative machine learning algorithm. A generative probabilistic model (LDA) was used to identify the essential topic in each cluster. This type of framework will empower the patients and doctors to identify the similarity and dissimilarity about the various diseases and important keywords among the diseases in the form of symptoms, medical tests and habits