The Effectivity of Enterotoxigenic Escherichia coli (Multivalen) Vaccination in Swine Case Study in Bali

Swine cattle have high economic advantages and social values ​​ in Balinese society. This study aimed to determine the effectiveness of Enterotoxigenic Escherichia coli (ETEC) vaccine in gestating sows. We used 26 gestating sows aged 1.5 years old at their last trimester assigning 13 sows in the control group and 13 sows in treatment group to receive multivalent ETEC vaccine twice: on the 70-75 days of gestation and a booster on 100-105 days of gestation. Sows with the vaccine treatment divided into 3 group that groups A was treated antifimbrial K41, groups B was antifimbrial 987P, while in group C was Antiimbrial K88. The changes in temperature were observed from one day before to 4 days after vaccination in a randomized block design. To determine the antibody formed, blood samples were taken one and two weeks after the first vaccine and five weeks after the booster. The blood sample was analyzed by the Enzyme Linked Immunosorbent Assay (ELISA) technique. The rates of diarrhea and postnatal mortality were also observed. The results showed that the antibody titer level increased significantly in the fifth week in groups A with titer 1,94 ±0,22 and B with titer 1,98 ± 0,30 , while the number of diarrhea incidents was 0.9% compared to control 34% with a mortality rate of 0%. In conclusion, this multivalent ETEC vaccine is safe to use and has been shown to be effective for ETEC cases in swine.

Varicella-zoster virus reactivation causing herpes zoster ophthalmicus (HZO) after SARS-CoV-2 vaccination – report of three cases

Purpose We are reporting 3 patients who presented acute zoster ophthalmicus (HZO), an activation of varicella-zoster virus, after mRNA anti-SARS-CoV-2 vaccination, seen directly or referred to our center. Cases A 73-year-old woman with history of ocular sarcoidosis presented HZO in the right V1 dermatome 16 days after a single booster dose of vaccination (Pfizer BioNTech). A 69-year-old woman presented HZO in her V1 left dermatome, occurring 10 days after her first dose of Pfizer BioNTech vaccine. A 72-year-old woman with no history of autoimmune pathology, candidate for cataract surgery, presented 13 days after the first dose of a Moderna mRNA vaccine with an eruption in the left V1 dermatome. All patients presented the VZV infection after their first dose of a mRNA type of vaccine. Treatment with Valacyclovir 1000 mg × 3/ day for 7–14 days was efficient in all cases. Conclusion Vaccines have been reported in the past to trigger different types of side effects such as viral or flu-like symptoms. It is only logical to note many different side effects for SARS-CoV-2 vaccines as the population vaccinated is exceeding any other number in history. VZV is one of the more severe side effects that can, however, be treated. It is quite obvious that, as far as mRNA vaccines are concerned, and probably also other anti-SARS-CoV-2 vaccines, that the benefit of vaccination certainly outweighs the possible but very low risk of ocular side effects that can mostly be treated.

Dissecting Tumor Antigens and Immune Subtypes of Glioma to Develop mRNA Vaccine

BackgroundNowadays, researchers are leveraging the mRNA-based vaccine technology used to develop personalized immunotherapy for cancer. However, its application against glioma is still in its infancy. In this study, the applicable candidates were excavated for mRNA vaccine treatment in the perspective of immune regulation, and suitable glioma recipients with corresponding immune subtypes were further investigated.MethodsThe RNA-seq data and clinical information of 702 and 325 patients were recruited from TCGA and CGGA, separately. The genetic alteration profile was visualized and compared by cBioPortal. Then, we explored prognostic outcomes and immune correlations of the selected antigens to validate their clinical relevance. The prognostic index was measured via GEPIA2, and infiltration of antigen-presenting cells (APCs) was calculated and visualized by TIMER. Based on immune-related gene expression, immune subtypes of glioma were identified using consensus clustering analysis. Moreover, the immune landscape was visualized by graph learning-based dimensionality reduction analysis.ResultsFour glioma antigens, namely ANXA5, FKBP10, MSN, and PYGL, associated with superior prognoses and infiltration of APCs were selected. Three immune subtypes IS1–IS3 were identified, which fundamentally differed in molecular, cellular, and clinical signatures. Patients in subtypes IS2 and IS3 carried immunologically cold phenotypes, whereas those in IS1 carried immunologically hot phenotype. Particularly, patients in subtypes IS3 and IS2 demonstrated better outcomes than that in IS1. Expression profiles of immune checkpoints and immunogenic cell death (ICD) modulators showed a difference among IS1–IS3 tumors. Ultimately, the immune landscape of glioma elucidated considerable heterogeneity not only between individual patients but also within the same immune subtype.ConclusionsANXA5, FKBP10, MSN, and PYGL are identified as potential antigens for anti-glioma mRNA vaccine production, specifically for patients in immune subtypes 2 and 3. In summary, this study may shed new light on the promising approaches of immunotherapy, such as devising mRNA vaccination tailored to applicable glioma recipients.

Alphaviruses: Host pathogenesis, immune response, and vaccine & treatment updates

Human pathogens belonging to the Alphavirus genus, in the Togaviridae family, are transmitted primarily by mosquitoes. The signs and symptoms associated with these viruses include fever and polyarthralgia, defined as joint pain and inflammation, as well as encephalitis. In the last decade, our understanding of the interactions between members of the alphavirus genus and the human host has increased due to the re-appearance of the chikungunya virus (CHIKV) in Asia and Europe, as well as its emergence in the Americas. Alphaviruses affect host immunity through cytokines and the interferon response. Understanding alphavirus interactions with both the innate immune system as well as the various cells in the adaptive immune systems is critical to developing effective therapeutics. In this review, we summarize the latest research on alphavirus-host cell interactions, underlying infection mechanisms, and possible treatments.

A Mini Review Medicinal plants with Antiviral properties against SARS-CoV-2

Background: The aim of the present project is to provide basic knowledge about the treatment of Coronavirus via medicinal plants. Coronavirus (COVID-19, SARS-CoV, and MERS-CoV) as a viral pneumonia causative agent, infects thousands of people worldwide. There is currently no specific medicine or vaccine available and it is considered a threat to develop effective novel drug or anti-coronavirus vaccine treatment. However, natural compounds to treat coronaviruses are the most alternative and complementary therapies due to their diverse range of biological and therapeutic properties. Coronaviruses have large viral RNA Genomes and are single-stranded positive-sense RNA viruses. The nsp10/nsp16 protein is an important target because it is essential for the virus to replicate, the papain-like protease (Nsp3), the main protease (Nsp5), the primary RNA-dependent RNA polymerase (Nsp12) are also attractive drug targets for this disease. The main aim of this review is gathering information about medicinal plants with antiviral properties from plant database.

A Neoantigen-Based Peptide Vaccine for Patients With Advanced Pancreatic Cancer Refractory to Standard Treatment

BackgroundNeoantigens are critical targets to elicit robust antitumor T-cell responses. Personalized cancer vaccines developed based on neoantigens have shown promising results by prolonging cancer patients’ overall survival (OS) for several cancer types. However, the safety and efficacy of these vaccine modalities remains unclear in pancreatic cancer patients.MethodsThis retrospective study enrolled 7 advanced pancreatic cancer patients. Up to 20 neoantigen peptides per patient identified by our in-house pipeline iNeo-Suite were selected, manufactured and administered to these patients with low tumor mutation burden (TMB) (less than 10 mutations/Mb). Each patient received multiple doses of vaccine depending on the progression of the disease. Peripheral blood samples of each patient were collected pre- and post-vaccination for the analysis of the immunogenicity of iNeo-Vac-P01 through ELISpot assay and flow cytometry.ResultsNo severe vaccine-related adverse effects were witnessed in patients enrolled in this study. The mean OS, OS associated with vaccine treatment and progression free survival (PFS) were reported to be 24.1, 8.3 and 3.1 months, respectively. Higher peripheral IFN-γ titer and CD4+ or CD8+ effector memory T cells count post vaccination were found in patients with relatively long overall survival. Remarkably, for patient P01 who had a 21-month OS associated with vaccine treatment, the abundance of antigen-specific TCR clone drastically increased from 0% to nearly 100%, indicating the potential of iNeo-Vac-P01 in inducing the activation of a specific subset of T cells to kill cancer cells.ConclusionsNeoantigen identification and selection were successfully applied to advanced pancreatic cancer patients with low TMB. As one of the earliest studies that addressed an issue in treating pancreatic cancer with personalized vaccines, it has been demonstrated that iNeo-Vac-P01, a personalized neoantigen-based peptide vaccine, could improve the currently limited clinical efficacy of pancreatic cancer.Clinical Trial RegistrationClinicalTrials.gov, identifier (NCT03645148).Registered August 24, 2018 - Retrospectively registered

Effects of Multivalent BRD Vaccine Treatment and Temperament on Performance and Feeding Behavior Responses to a BVDV1b Challenge in Beef Steers

This study examined the effects of multivalent respiratory vaccine treatment (VT) and animal temperament classification on feeding behavior traits, feed intake and animal performance in response to a bovine viral diarrhea virus (BVDV) challenge. Nellore–Angus crossbred steers (n = 360; initial body weight (BW) 330 ± 48 kg) were assigned to one of three vaccine treatments: non-vaccinated (NON), modified live (MLV) and killed (KV) regarding respiratory viral pathogens, and inoculated intranasally with the same BVDV1b strain. Cattle temperament categories were based on exit velocity. Overt clinical signs of respiratory disease were not observed, yet the frequency and duration of bunk visit events as well as traditional performance traits decreased (p < 0.01) following BVDV challenge and then rebounded in compensatory fashion. The reduction in dry matter intake (DMI) was less (p < 0.05) for MLV-vaccinated steers, and MLV-vaccinated steers had longer (p < 0.01) durations of bunk visit and meal events and slower (p < 0.01) eating rates compared with KV- and non-vaccinated steers following BVDV challenge. Greater differences in most feeding behavior traits due to VT existed within calm vs. excitable steers. Respiratory vaccination can reduce the sub-clinical feeding behavior and performance effects of BVDV in cattle, and the same impacts may not occur across all temperament categories.

A peptide-based neoantigen vaccine for patients with advanced pancreatic cancer refractory to standard treatment.

e14563 Background: Tumor-specific neoantigens are considered as personalized and potential ultimate targets for cancer immunotherapy. Recently, neoantigen cancer vaccines have been designed to train the patient's immune system to specifically target and kill tumor cells. However, the safety and efficacy of neoantigen vaccines in pancreatic cancer treatment remain poorly understood. Methods: Personalized peptide neoantigen cancer vaccines were successfully designed and manufactured for pancreatic cancers with low tumor mutation burden. Seven patients with advanced pancreatic cancer refractory to standard treatments were enrolled and treated with personalized peptide neoantigen vaccine, iNeo-Vac-P01. Besides the evaluation of the safety and clinical efficacy of iNeo-Vac- P01, pre- and post-vaccination peripheral blood samples were collected to analyze the vaccine’s immunogenicity. Results: For all 7 patients, none sever vaccine-related adverse effects was witnessed. The mean progression free survival, overall survival (OS) and OS associated with vaccine treatment were 3.1, 24.1 and 8.3 months, respectively. For Patient P01, who had a 21-month OS associated with vaccine treatment, the abundance of the TCR clone remarkably increased after vaccination, indicating the potential of iNeo-Vac-P01 to specifically induce a subset of T cells to kill tumor cells. This study also demonstrated that the quantity of IFN-γ in peripheral blood might be a potential biomarker for OS. Conclusions: We believed that it was the first tentative study focused in the application of peptide-based neoantigen cancer vaccine in advanced pancreatic cancer. Promisingly, personalized peptide neoantigen vaccine might provide a new strategy to improve the limited clinical efficacy for pancreatic cancer. Clinical trial information: NCT03645148.

Analysis of COVID-19 on Diagnosis, Vaccine, Treatment, and Pathogenesis with Clinical Scenarios

As the world continues to suffer from an ever-growing number of confirmed cases of the SARS-CoV-2 novel coronavirus, researchers are at the forefront of developing the best plan to overcome this pandemic through analyzing the pathogenesis, prevention, and treatment options pertaining to the virus. In the midst of a pandemic, the main route for detection of the virus has been conducting antigen tests for rapid results, using qRT-PCR, and conducting more accurate molecular tests, using rRT-PCR, on samples from patients. Most common treatments for those infected with COVID-19 include Remdesivir, an antiviral, dexamethasone, a steroid, and rarely, monoclonal antibody treatments. Although these treatments exist and are used commonly in hospitals all around the globe, clinicians often challenge the efficacy and benefit of these remedies for the patient. Furthermore, targeted therapies largely focus on interfering with or reducing the binding of viral receptors and host cell receptors affected by the SARS-CoV-2 novel coronavirus. In addition to treatment, the most efficacious method of preventing the spread of COVID-19 is the development of multiple vaccines that have been distributed as well as the development of multiple vaccine candidates that are proving hopeful in preventing severe symptoms of the virus. The exaggerated immune response to the virus proves to be a worrying complication due to widespread inflammation and subsequent clinical sequela. The medical and scientific community as a whole will be expected to respond with the latest in technology and research, and further studies into the pathogenesis, clinical implications, identification, diagnosis, and treatment of COVID-19 will push society past this pandemic.

Longitudinal in vivo imaging of acute neuropathology in a monkey model of Ebola virus infection

Ebola virus (EBOV) causes neurological symptoms yet its effects on the central nervous system (CNS) are not well-described. Here, we longitudinally assess the acute effects of EBOV on the brain, using quantitative MR-relaxometry, 18F-Fluorodeoxyglucose PET and immunohistochemistry in a monkey model. We report blood–brain barrier disruption, likely related to high cytokine levels and endothelial viral infection, with extravasation of fluid, Gadolinium-based contrast material and albumin into the extracellular space. Increased glucose metabolism is also present compared to the baseline, especially in the deep gray matter and brainstem. This regional hypermetabolism corresponds with mild neuroinflammation, sporadic neuronal infection and apoptosis, as well as increased GLUT3 expression, consistent with increased neuronal metabolic demands. Neuroimaging changes are associated with markers of disease progression including viral load and cytokine/chemokine levels. Our results provide insight into the pathophysiology of CNS involvement with EBOV and may help assess vaccine/treatment efficacy in real time.