Cell culture-derived influenza vaccines from Vero cells: a new horizon for vaccine production

In the 20th century, three influenza pandemics killed approximately 100 million people. The traditional method of influenza vaccine manufacturing is based on using chicken eggs. However, the necessity of the availability of millions of fertile eggs in the event of a pandemic has led research to focus on the development of cell culture-derived vaccines, which offer shorter lead-in times and greater flexibility of production. So far, the cell substrates being evaluated and in use include Vero, Madin-Darby canine kidney, PER.C6 and insect cells. However, Vero cells are the most widely accepted among others. This review introduces briefly the concepts of advanced cell culture-derived influenza vaccine production and highlights the advantages of these vaccines in terms of efficiency, speed and immunogenicity based on the clinical data obtained from different studies.     

Treatment of Evan’s syndrome by leflunomide and desmopressin in a mixed-breed dog

A 9-year-old, male, mixed-breed dog was presented with severe lethargy, pale and icterus mucous membranes, gingival hemorrhage, and hematochezia. On physical examination, petechiae and echimosis on the penis were observed. The complete blood count revealed severe regenerative anemia and thrombocytopenia. Urinalysis indicated hemoglobinuria and bilirobinuria, and abdominal sonography showed splenomegaly. A series of diagnostic tests was performed based on the suspicion of Evan’s syndrome (concurrent immune-mediated anemia and thrombocytopenia). The therapeutic program was started with prednisolone combined with leflunomide followed by desmopressin and erythropoietin, lasted 1?month, and the animal showed progressive recovery. During 6?months follow-up, no complications were detected in the mentioned case.     

The comparison of visfatin levels of gingival crevicular fluid in systemic lupus erythematosus and chronic periodontitis patients with healthy subjects

Clinical Rheumatology - Visfatin is an adipokine and has a crucial role in pro-inflammatory response. The aim of this study was investigating the visfatin levels of gingival crevicular fluid (GCF)...     

Serological evidence of canine monocytic ehrlichiosis in Iran

Ehrlichia canis has a worldwide geographic distribution, but little is known about the occurrence of Canine monocytic ehrlichiosis (CME) in Iran. The current study was carried out to evaluate the seroprevalence and factors associated with a positive antibody response to E. canis in dogs from Kerman city, southeast of Iran. One hundred and twenty-three privately owned dogs were chosen from apparently healthy animals referred to veterinary hospital for health check or vaccination. All dogs were subjected to physical, hematological, and biochemical examinations and serological tests. Indirect immunofluorescence antibody test (IFA) and rapid immunochromatography assay (ICA) used to detect antibodies against E. canis in all sera. The overall seroprevalence of CME was 14.63% which was determined as 13.8% and 10.6% using IFA and ICA, respectively. Hyperglobulinemia (p = 0.001), age (p = 0.005), and elevated alkaline phosphatase (ALP) level (p = 0.02) showed a statistical relationship with seropositivity. Hematological abnormalities did not differ significantly between seronegative and seropositive dogs except for the group with high IFA titer. In blood smears from three infected dogs (16.66%), typical morulae of E. canis were observed in monocytes. All three cases were seropositive for E. canis and displayed obvious hyperglobulinemia, thrombocytopenia, leukopenia, anemia, and high ALP level. There was no sex and breed predilection among seropositive dogs. This is the first report that describes serological evidences of canine monocytic ehrlichiosis in southeast of Iran. Additional molecular studies are necessary to confirm E. canis infection and to identify the local strains of the organism.     

International external quality assurance for laboratory identification and typing of Streptococcus agalactiae (Group B streptococci)

We report the results from the first international multicenter external quality assessment (EQA) studies for molecular and serological typing of group B streptococcus (GBS) strains as part of DEVANI (Design of a Vaccine against Neonatal Infections), a pan-European program. A questionnaire-based surveillance was undertaken among eight laboratories participating in DEVANI and six laboratories not participating in DEVANI from 13 countries in order to assess their current microbiological procedures for GBS screening, diagnosis, and typing. GBS strains from three EQA distributions were characterized using molecular and serological methods based on GBS capsular polysaccharide typing. Participants were asked to test the first distribution using their current serotyping and genotyping methods. The Strep-B-Latex agglutination method was the most widely used method, with a typeability value of >90%. A multiplex PCR assay for GBS capsular gene typing was also used by 2 of 14 centers, which achieved a typeability value of 93%; this assay detected only 9 of 10 GBS capsular polysaccharide genes. From the second and third EQA studies, standardized protocols were prepared for serological and molecular typing of GBS strains based on the Strep-B-Latex agglutination method and a novel multiplex PCR assay that detected all 10 GBS capsular types (Ia to IX). These standardized protocols are being used by many European laboratories, and as the use of these methods increases, it is imperative to continuously improve and assess laboratory performance and offer training to any laboratories that have technical difficulties.     

Interaction of histamine and calcitonin gene-related peptide in the formalin induced pain perception in rats

Histamine and calcitonin gene-related peptide (CGRP) contribute to the pain perception. The aim of the present study is to clarify the interaction of histamine and CGRP in the perception of inflammatory pain. The effects of a histamine H1 receptor antagonist (pyrilamine, i.p.), an H2 receptor antagonist (ranitidine, i.p.) and a CGRP antagonist (CGRP 8-37, i.t.) on the formalininduced pain was studied in rats. Pyrilamine and ranitidine produced a dose-dependent antinociceptive response in the first and the second phases of the formalin test. A single administration of pyrilamine (1 mg/kg, i.p.), ranitidine (10 mg/kg, i.p.) or CGRP 8-37 (10 μg/μL, i.t.) had no significant effects on the pain perception in the second phase. A combination of CGRP 8-37 and pyrilamine or ranitidine at these sub-effective doses, however, showed nociceptive response in the second phase. Moreover, a histamine (i.t.)-induced hyperalgesia was completely prevented by treatment with GGRP 8-37 at this dose. Our findings have raised the possibility that the CGRP system has interaction with histamine in the perception of inflammatory pain.     

Current adjuvants and new perspectives in vaccine formulation

Given the important role of adjuvants in prophylactic vaccines, identification and development of new adjuvants with enhanced efficacy and safety is necessary. The use of adjuvants with immunopotentiating properties that can direct the immune responses to humoral or cell-mediated immunity and can induce T-cell responses has made it possible to design more protective vaccines. Although current regulations focus on traditional adjuvants, notably aluminum and calcium salts, advances have been made in regulatory considerations. The regulatory agencies for the evaluation of medicinal products are actively drafting guidance on requirements for the evaluation of new adjuvants. This article briefly summarizes the most widely studied adjuvants in vaccination, including those licensed for human vaccines and the regulatory aspects relevant to adjuvant quality at development stages.     

Effect of polyethylene glycol coatings on uptake of indocyanine green loaded nanocapsules by human spleen macrophages in vitro

Near-infrared (NIR) optically active nanoparticles are promising exogenous chromophores for applications in medical imaging and phototherapy. Since nanoparticles can be rapidly eliminated from the body by cells of the reticuloendothelial system, a thriving strategy to increase their blood circulation time is through surface modification with polyethylene glycol (PEG). We constructed polymeric nanocapsules loaded with indocyanine green (ICG), an FDA-approved NIR dye, and coated with aldehyde-terminated PEG. Using optical absorbance spectroscopy and flow cytometry, we investigated the effect of PEG coating and molecular weight (MW) of PEG [5000 and 30,000 Daltons (Da)] on the phagocytic content of human spleen macrophages incubated with ICG-containing nanocapsules (ICG-NCs) between 15 to 360 min. Our results indicate that surface coating with PEG is an effective method to reduce the phagocytic content of ICG-NCs within macrophages for at least up to 360 min of incubation time. Coating the surface of ICG-NCs with the low MW PEG results in lower phagocytic content of ICG-NCs within macrophages for at least up to 60 min of incubation time as compared to ICG-NCs coated with the high MW PEG. Surface coating of ICG-NCs with PEG is a promising approach to prolong vasculature circulation time of ICG for NIR imaging and phototherapeutic applications.     

Updated consensus guidelines on the management of Phelan–McDermid syndrome

Phelan–McDermid syndrome (PMS) is a genetic condition caused by SHANK3 haploinsufficiency and characterized by a wide range of neurodevelopmental and systemic manifestations. The first practice parameters for assessment and monitoring in individuals with PMS were published in 2014; recently, knowledge about PMS has grown significantly based on data from longitudinal phenotyping studies and large-scale genotype–phenotype investigations. The objective of these updated clinical management guidelines was to: (1) reflect the latest in knowledge in PMS and (2) provide guidance for clinicians, researchers, and the general community. A taskforce was established with clinical experts in PMS and representatives from the parent community. Experts joined subgroups based on their areas of specialty, including genetics, neurology, neurodevelopment, gastroenterology, primary care, physiatry, nephrology, endocrinology, cardiology, gynecology, and dentistry. Taskforce members convened regularly between 2021 and 2022 and produced specialty-specific guidelines based on iterative feedback and discussion. Taskforce leaders then established consensus within their respective specialty group and harmonized the guidelines. The knowledge gained over the past decade allows for improved guidelines to assess and monitor individuals with PMS. Since there is limited evidence specific to PMS, intervention mostly follows general guidelines for treating individuals with developmental disorders. Significant evidence has been amassed to guide the management of comorbid neuropsychiatric conditions in PMS, albeit mainly from caregiver report and the experience of clinical experts. These updated consensus guidelines on the management of PMS represent an advance for the field and will improve care in the community. Several areas for future research are also highlighted and will contribute to subsequent updates with more refined and specific recommendations as new knowledge accumulates.