Immunogenicity and protective efficacy of adenoviral and subunit RSV vaccines based on stabilized prefusion F protein in pre-clinical models

Respiratory Syncytial Virus (RSV) remains a leading cause of severe respiratory disease for which no licensed vaccine is available. We have previously described the derivation of an RSV Fusion protein (F) stabilized in its prefusion conformation (preF) as vaccine immunogen and demonstrated superior immunogenicity in naive mice of preF versus wild type RSV F protein, both as protein and when expressed from an Ad26 vaccine vector. Here we address the question if there are qualitative differences between the two vaccine platforms for induction of protective immunity. In naïve mice, both Ad26.RSV.preF and preF protein induced humoral responses, whereas cellular responses were only elicited by Ad26.RSV.preF. In RSV pre-exposed mice, a single dose of either vaccine induced cellular responses and strong humoral responses. Ad26-induced RSV-specific cellular immune responses were detected systemically and locally in the lungs. Both vaccines showed protective efficacy in the cotton rat model, but Ad26.RSV.preF conferred protection at lower virus neutralizing titers in comparison to RSV preF protein. Factors that may contribute to the protective capacity of Ad26.RSV.preF elicited immunity are the induced IgG2a antibodies that are able to engage Fcγ receptors mediating Antibody Dependent Cellular Cytotoxicity (ADCC), and the induction of systemic and lung resident RSV specific CD8 + T cells. These data demonstrate qualitative improvement of immune responses elicited by an adenoviral vector based vaccine encoding the RSV preF antigen compared to the subunit vaccine in small animal models which may inform RSV vaccine development.     

Murine models of posterolateral spinal fusion: A systematic review

BackgroundRodent models are commonly used experimentally to assess treatment effectiveness in spinal fusion. Certain factors are associated with better fusion rates. The objectives of the present study were to report the protocols most frequently used, to evaluate factors known to positively influence fusion rate, and to identify new factors.MethodA systematic literature search of PubMed and Web of Science found 139 experimental studies of posterolateral lumbar spinal fusion in rodent models. Data for level and location of fusion, animal strain, sex, weight and age, graft, decortication, fusion assessment and fusion and mortality rates were collected and analyzed.ResultsThe standard murine model for spinal fusion was male Sprague Dawley rats of 295 g weight and 13 weeks’ age, using decortication, with L4-L5 as fusion level. The last two criteria were associated with significantly better fusion rates. On manual palpation, the overall mean fusion rate in rats was 58% and the autograft mean fusion rate was 61%. Most studies evaluated fusion as a binary on manual palpation, and only a few used CT and histology. Average mortality was 3.03% in rats and 1.56% in mice.ConclusionsThese results suggest using a rat model, younger than 10 weeks and weighing more than 300 grams on the day of surgery, to optimize fusion rates, with decortication before grafting and fusing the L4-L5 level.     

Selective blocking laminoplasty in cervical laminectomy and fusion to prevent postoperative C5 palsy

BACKGROUND CONTEXT

Cervical laminectomy and fusion (CLF) is a common surgical option for multilevel cord compression. Postoperative C5 palsy occurrence after CLF has been a vexing problem for spine physicians. The posterior shift of the cord following laminectomy has been implicated as a major factor for postoperative C5 palsy, but attempts by spine surgeons to mitigate excessive shift while providing sufficient decompression have not been well reported.

Microscopia confocal ex vivo con método de fusión y tinción digital: cambiando paradigmas en el diagnóstico histológico

The ex vivo confocal microscope is an imaging system designed to analyze freshly excised tissue using two diode lasers with different wavelengths. The technique can dramatically reduce margin analysis times and offers a sensitivity of 88% and a specificity of 89% relative to histopathology. A new technology has recently been developed that produces images more quickly and with a higher resolution than before. By means of a fusion mode that combines simultaneously scanned fluorescence and reflectance images, it produces digitally stained images that simulate the effect of hematoxylin-eosin staining. Application of this new technology has opened the door to real-time tissue diagnostics.     

Fusion imaging to evaluate the radiographic anatomical relationship between primary tumors and local recurrences in retroperitoneal soft tissue sarcoma

BackgroundLocal recurrence (LR) of retroperitoneal soft tissue sarcoma (RPS) is a common and life-threatening event. The evaluation of the exact anatomical patterns of local recurrence might help to improve local treatment in RPS.MethodsOf our local database we extracted ten patients with LR of RPS with axial MRI and/or CT datasets of the primary tumor (PT) and the LR. Using the Osirix DICOM viewer Version v.3.9.4 64-bit (Pixmeo, Geneva, Switzerland) we performed a three-step fusion algorithm consisting of: a) 3-point co-registration of the axial datasets depicting the PT and the LR using three abdominal landmarks b) re-orientation of the datasets and c) image fusion. We evaluated the feasibility of this technique with regard to categorizing the localization of LR as within or distant from the PT.ResultsFusion imaging was feasible in seven out of ten patients. In the other three patients anatomical shifting of organs after surgery led to a relevant mismatch of anatomical landmarks and impeded interpretation of the fused images. In five of seven patients with successful fusion imaging, local recurrences were located within the anatomical borders of the primary tumor, in two out of seven patients local recurrences were distant to the primary.ConclusionsFusion imaging of primary tumors and local recurrences is feasible in most patients with RPS. Most local recurrences occurred within the anatomical localization of the primary tumor. For further investigations validation of the technique in larger patient cohorts is required.