scholarly journals Immunological Characterization of the Chemically Prepared Ghosts of Salmonella Typhimurium as a Vaccine Candidate

2021 ◽  
Author(s):  
Sameh Rabea ◽  
Aymen S. Yassin ◽  
Aly Fahmy Mohammed ◽  
Mounir M. Salem-Bekhit ◽  
Fars K. Alanazi ◽  
...  
Keyword(s):  
Immune Response ◽  
Salmonella Typhimurium ◽  
Vaccine Candidate ◽  
Bacterial Load ◽  
Survival Rates ◽  
Liver Homogenate ◽  
Maximum Level ◽  
Effective Vaccine ◽  
High Survival ◽  
Bacterial Ghosts

Abstract Background: The purpose of this study is to measure the immunogenic protective response of bacterial ghosts of Salmonella typhimurium in animals. Accordingly, the researchers will be able to do further clinical trials and confirm the efficiency of bacterial ghosts in human vaccination. The targets to be measured are humoral immune response: immunoglobulins elevation (IgG), cellular immune response: granulocytes increment; serum antibacterial activity; success the faeces and liver virulence challenge and High survival rates.Results: The BG vaccine was able to protect 100% of BG subcutaneously vaccinated rats and 75% of BG-adjuvant subcutaneously vaccinated rats. The lowest survival rate was in the BG orally vaccinated group (25%). The maximum level of serum IgG titers as well as serum and faeces bactericidal activity (100% eradication) was exhibited in the subcutaneously vaccinated group with BG-adjuvant followed by the BG subcutaneously vaccinated one. Additionally, the highest granulocytes’ number was observed in the BG-adjuvant subcutaneously immunized group. The bacterial load in liver homogenate eliminated in the subcutaneously vaccinated rats by BG after virulence challenge. Conclusions: The bacterial ghosts of Salmonella enterica serovar Typhimurium that prepared by tween 80 protocol showed an effective vaccine candidate that protected animals, eliminated the virulence in faeces and liver. These findings suggest that chemically induced bacterial ghosts of Salmonella typhimurium can be a promising vaccine.

scholarly journals A Prime-Boost Strategy Using the Novel Vaccine Candidate, LemA, Protects Hamsters against Leptospirosis

2013 ◽  
Vol 20 (5) ◽  
pp. 747-752 ◽  
Author(s):  
Daiane D. Hartwig ◽  
Karine M. Forster ◽  
Thaís L. Oliveira ◽  
Marta Amaral ◽  
Alan J. A. McBride ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Response ◽  
Dna Vaccine ◽  
Subunit Vaccine ◽  
Vaccine Candidate ◽  
Virulent Strain ◽  
Effective Vaccine ◽  
Pairwise Identity ◽  
Content Type ◽  
Vaccine Preparation

ABSTRACTToward developing an effective vaccine capable of conferring heterologous protection, the putative lipoprotein LemA, which presents an M3 epitope similar to that ofListeria, was evaluated as a vaccine candidate in the hamster model of leptospirosis. LemA is conserved (>70% pairwise identity) among the pathogenicLeptospiraspp., indicating its potential in stimulating a cross-protective immune response. Using different vaccination strategies, including prime-boost, DNA vaccine, and a subunit preparation, recombinant LemA conferred different levels of protection in hamsters. Significant protection against mortality was observed for the prime-boost and the DNA vaccine strategies, which showed 87.5% (P< 0.01) and 62.5% (P< 0.05) efficacy, respectively. Although the subunit vaccine preparation protected 50.0% of immunized hamsters, the level of protection was not significant. None of the hamsters in the control groups survived challenge with a virulent strain ofLeptospira interrogansserogroup Icterohaemorrhagiae. Characterization of the immune response found that the strongest antibody response was stimulated by the subunit vaccine preparation, followed by the prime-boost strategy. The DNA vaccine failed to elicit an antibody response in immunized hamsters.

scholarly journals A Review of the Animal and Human Trials of the Ad5-nCoV Vaccine Candidate

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Cheng En Xi ◽  
Jasrita Singh
Keyword(s):  
Immune Response ◽  
Vaccine Candidate ◽  
Recombinant Adenovirus ◽  
Neutralizing Antibody ◽  
Effective Vaccine ◽  
Strong Immune Response ◽  
Human Trials ◽  
Search Terms ◽  
Global Pandemic ◽  
Pubmed Database

Since the COVID-19 outbreak began, there has been an urgent need for a safe and effective vaccine to end this global pandemic. One such vaccine is the Ad5-nCoV, developed by CanSino Biologics Inc. This review aims to examine all animal and human trials conducted for this vaccine candidate. Search terms such as “Ad5-nCoV”, “recombinant adenovirus”, “COVID-19”, and “vaccine”, were used in varying combinations in the PubMed database to find published trial reports. It was concluded that Ad5-nCoV can induce a strong immune response in mice and ferret models and offer them protection against the inoculation of SARS-CoV-2. It also has a strong safety profile in human and can induce an adequate immune response in terms of RBD-specific antibodies and T cell responses, while neutralizing antibody response and seroconversion was mediocre. The publish trial reports support the further testing of this vaccine candidate and it is preparing to enter phase 3 clinical trials.

scholarly journals Cognitive decline in patients with prostate cancer: study protocol of a prospective cohort, NEON-PC

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e043844
Author(s):  
Natalia Araujo ◽  
Samantha Morais ◽  
Ana Rute Costa ◽  
Raquel Braga ◽  
Ana Filipa Carneiro ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Androgen Deprivation Therapy ◽  
Survival Rates ◽  
Cardiovascular Complications ◽  
Androgen Deprivation ◽  
High Survival ◽  
The Impact

IntroductionProstate cancer is the most prevalent oncological disease among men in industrialised countries. Despite the high survival rates, treatments are often associated with adverse effects, including metabolic and cardiovascular complications, sexual dysfunction and, to a lesser extent, cognitive decline. This study was primarily designed to evaluate the trajectories of cognitive performance in patients with prostate cancer, and to quantify the impact of the disease and its treatments on the occurrence of cognitive decline.MethodsParticipants will be recruited from two main hospitals providing care to approximately half of the patients with prostate cancer in Northern Portugal (Portuguese Institute of Oncology of Porto and São João Hospital Centre), and will comprise a cohort of recently diagnosed patients with prostate cancer proposed for different treatment plans, including: (1) radical prostatectomy; (2) brachytherapy and/or radiotherapy; (3) radiotherapy in combination with androgen deprivation therapy and (4) androgen deprivation therapy (with or without chemotherapy). Recruitment began in February 2018 and is expected to continue until the first semester of 2021. Follow-up evaluations will be conducted at 1, 3, 5, 7 and 10 years. Sociodemographic, behavioural and clinical characteristics, anxiety and depression, health literacy, health status, quality of life, and sleep quality will be assessed. Blood pressure and anthropometrics will be measured, and a fasting blood sample will be collected. Participants’ cognitive performance will be evaluated before treatments and throughout follow-up (Montreal Cognitive Assessment and Cube Test as well as Brain on Track for remote monitoring). All participants suspected of cognitive impairment will undergo neuropsychological tests and clinical observation by a neurologist.Ethics and disseminationThe study was approved by the Ethics Committee of the hospitals involved. All participants will provide written informed consent, and study procedures will be developed to ensure data protection and confidentiality. Results will be disseminated through publication in peer-reviewed journals and presentation in scientific meetings.

scholarly journals A Whole Virion Vaccine for COVID-19 Produced via a Novel Inactivation Method and Preliminary Demonstration of Efficacy in an Animal Challenge Model

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 340
Author(s):  
Izabela K Ragan ◽  
Lindsay M Hartson ◽  
Taru S Dutt ◽  
Andres Obregon-Henao ◽  
Rachel M Maison ◽  
...  
Keyword(s):  
Vaccine Candidate ◽  
Rapid Development ◽  
Neutralizing Antibody ◽  
Emerging Diseases ◽  
Effective Vaccine ◽  
Preliminary Evaluation ◽  
Sequencing Data ◽  
Post Challenge ◽  
Vaccine Candidates ◽  
The Impact

The COVID-19 pandemic has generated intense interest in the rapid development and evaluation of vaccine candidates for this disease and other emerging diseases. Several novel methods for preparing vaccine candidates are currently undergoing clinical evaluation in response to the urgent need to prevent the spread of COVID-19. In many cases, these methods rely on new approaches for vaccine production and immune stimulation. We report on the use of a novel method (SolaVAX) for production of an inactivated vaccine candidate and the testing of that candidate in a hamster animal model for its ability to prevent infection upon challenge with SARS-CoV-2 virus. The studies employed in this work included an evaluation of the levels of neutralizing antibody produced post-vaccination, levels of specific antibody sub-types to RBD and spike protein that were generated, evaluation of viral shedding post-challenge, flow cytometric and single cell sequencing data on cellular fractions and histopathological evaluation of tissues post-challenge. The results from this preliminary evaluation provide insight into the immunological responses occurring as a result of vaccination with the proposed vaccine candidate and the impact that adjuvant formulations, specifically developed to promote Th1 type immune responses, have on vaccine efficacy and protection against infection following challenge with live SARS-CoV-2. This data may have utility in the development of effective vaccine candidates broadly. Furthermore, the results of this preliminary evaluation suggest that preparation of a whole virion vaccine for COVID-19 using this specific photochemical method may have potential utility in the preparation of one such vaccine candidate.

scholarly journals Autophagy—A Story of Bacteria Interfering with the Host Cell Degradation Machinery

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 110
Author(s):  
Anna K. Riebisch ◽  
Sabrina Mühlen ◽  
Yan Yan Beer ◽  
Ingo Schmitz
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Immune Response ◽  
Mycobacterium Tuberculosis ◽  
Listeria Monocytogenes ◽  
Salmonella Typhimurium ◽  
Innate Immune ◽  
Intracellular Pathogens ◽  
Response Mechanism ◽  
Pathogenic Escherichia Coli

Autophagy is a highly conserved and fundamental cellular process to maintain cellular homeostasis through recycling of defective organelles or proteins. In a response to intracellular pathogens, autophagy further acts as an innate immune response mechanism to eliminate pathogens. This review will discuss recent findings on autophagy as a reaction to intracellular pathogens, such as Salmonella typhimurium, Listeria monocytogenes, Mycobacterium tuberculosis, Staphylococcus aureus, and pathogenic Escherichia coli. Interestingly, while some of these bacteria have developed methods to use autophagy for their own benefit within the cell, others have developed fascinating mechanisms to evade recognition, to subvert the autophagic pathway, or to escape from autophagy.

scholarly journals Increased VEGF-A in solid type of lung adenocarcinoma reduces the patients’ survival

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Woon Yong Jung ◽  
Kyueng-Whan Min ◽  
Young Ha Oh
Keyword(s):  
Immune Response ◽  
Survival Analysis ◽  
Lung Adenocarcinoma ◽  
Survival Rates ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
Genetic Alterations ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Solid Type

AbstractThe histological classification of lung adenocarcinoma includes 5 types: lepidic, acinar, papillary, micropapillary and solid. The complex gene interactions and anticancer immune response of these types are not well known. The aim of this study was to reveal the survival rates, genetic alterations and immune activities of the five histological types and provide treatment strategies. This study reviewed the histological findings of 517 patients with lung adenocarcinoma from The Cancer Genome Atlas (TCGA) database and classified them into five types. We performed gene set enrichment analysis (GSEA) and survival analysis according to the different types. We found six oncogenic gene sets that were higher in lung adenocarcinoma than in normal tissues. In the survival analysis of each type, the acinar type had a favorable prognosis, and the solid subtype had an unfavorable prognosis; however, the survival differences between the other types were not significant. Our study focused on the solid type, which had the poorest prognosis. The solid type was related to adaptive immune resistance associated with elevated CD8 T cells and high CD274 (encoding PD-L1) expression. In the pathway analyses, the solid type was significantly related to high vascular endothelial growth factor (VEGF)-A expression, reflecting tumor angiogenesis. Non-necrosis/low immune response affected by high VEGF-A was associated with worse prognosis. The solid type associated with high VEGF-A expression may contribute to the development of therapeutic strategies for lung adenocarcinoma.

The effect of oxyclozanide on Hymenolepis microstoma and H. diminuta

Parasitology ◽  
1973 ◽  
Vol 66 (2) ◽  
pp. 355-365 ◽  
Author(s):  
C. A. Hopkins ◽  
P. M. Grant ◽  
Helen Stallard
Keyword(s):  
Immune Response ◽  
Small Intestine ◽  
Single Dose ◽  
Bile Duct ◽  
Dose Level ◽  
Harmful Effect ◽  
Maximum Level ◽  
Adult Size ◽  
Hymenolepis Microstoma

The effect of oxyclozanide (2,2′-dihydroxy-3,3′,5,5′,6-pentachlorobenzanilide) on Hymenolepis microstoma in the bile duct of mice, and H. diminuta in the small intestine of mice and rats was measured. Oxyclozanide at doses as low as 4mg/kg removed 13-day-old H. diminuta and caused no obvious harmful effect to the rat host up to the maximum level (256 mg/kg) tested. Worms were displaced and degenerating within 1 h. Results in mice were more difficult to assess because of the immune response, but similar total amounts of oxyclozanide caused destrobilation and loss of 7-day-old H. diminuta. Oxyclozanide was less effective against 21-day-old H. microstoma attached in the bile duct. Approximately half the strobila was lost following dosing at 5 mg/kg and progressively greater amounts as the dose level was increased. At 50 mg/kg worm loss commenced but even at 150 mg/kg 25 % of worms survived. The time taken to regrow to the original adult size varied but was complete within 7–9 days at levels up to 25 mg/kg. Double dosing at 5-day intervals did not enhance the effect of a single dose. The apparent existence of a sensitivity gradient down the strobila in H. microstoma is discussed.

scholarly journals Bone marrow niche crosses paths with BMPs: a road to protection and persistence in CML

2019 ◽  
Vol 47 (5) ◽  
pp. 1307-1325 ◽  
Author(s):  
Caroline Busch ◽  
Helen Wheadon
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Bone Morphogenetic Proteins ◽  
Kinase Inhibitor ◽  
Survival Rates ◽  
High Survival ◽  
Bone Marrow Niche ◽  
Matrix Deposition ◽  
Bmp Receptors ◽  
Number Of Patients

Abstract Chronic myeloid leukaemia (CML) is a paradigm of precision medicine, being one of the first cancers to be treated with targeted therapy. This has revolutionised CML therapy and patient outcome, with high survival rates. However, this now means an ever-increasing number of patients are living with the disease on life-long tyrosine kinase inhibitor (TKI) therapy, with most patients anticipated to have near normal life expectancy. Unfortunately, in a significant number of patients, TKIs are not curative. This low-level disease persistence suggests that despite a molecularly targeted therapeutic approach, there are BCR-ABL1-independent mechanisms exploited to sustain the survival of a small cell population of leukaemic stem cells (LSCs). In CML, LSCs display many features akin to haemopoietic stem cells, namely quiescence, self-renewal and the ability to produce mature progeny, this all occurs through intrinsic and extrinsic signals within the specialised microenvironment of the bone marrow (BM) niche. One important avenue of investigation in CML is how the disease highjacks the BM, thereby remodelling this microenvironment to create a niche, which enables LSC persistence and resistance to TKI treatment. In this review, we explore how changes in growth factor levels, in particular, the bone morphogenetic proteins (BMPs) and pro-inflammatory cytokines, impact on cell behaviour, extracellular matrix deposition and bone remodelling in CML. We also discuss the challenges in targeting LSCs and the potential of dual targeting using combination therapies against BMP receptors and BCR-ABL1.

scholarly journals Survival Rate of 1008 Short Dental Implants with 21 Months of Average Follow-Up: A Retrospective Study

2020 ◽  
Vol 9 (12) ◽  
pp. 3943
Author(s):  
João Caramês ◽  
Ana Catarina Pinto ◽  
Gonçalo Caramês ◽  
Helena Francisco ◽  
Joana Fialho ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Survival Rate ◽  
Dental Implants ◽  
Cox Regression ◽  
Survival Rates ◽  
High Survival ◽  
Implant Survival ◽  
Posterior Maxilla ◽  
Clinical Records

This retrospective study evaluated the survival rate of short, sandblasted acid-etched surfaced implants with 6 and 8 mm lengths with at least 120 days of follow-up. Data concerning patient, implant and surgery characteristics were retrieved from clinical records. Sandblasted and acid-etched (SLA)-surfaced tissue-level 6 mm (TL6) or 8 mm (TL8) implants or bone-level tapered 8 mm (BLT8) implants were used. Absolute and relative frequency distributions were calculated for qualitative variables and mean values and standard deviations for quantitative variables. A Cox regression model was performed to verify whether type, length and/or width influence the implant survival. The cumulative implant survival rate was assessed by time-to-event analyses (Kaplan–Meier estimator). In all, 513 patients with a mean age of 58.00 ± 12.44 years received 1008 dental implants with a mean follow-up of 21.57 ± 10.77 months. Most implants (78.17%) presented a 4.1 mm diameter, and the most frequent indication was a partially edentulous arch (44.15%). The most frequent locations were the posterior mandible (53.97%) and the posterior maxilla (31.55%). No significant differences were found in survival rates between groups of type, length and width of implant with the cumulative rate being 97.7% ± 0.5%. Within the limitations of this study, the evaluated short implants are a predictable option with high survival rates during the follow-up without statistical differences between the appraised types, lengths and widths.

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