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.     

Retroperitoneal-first laparoscopic approach (Retlap)-assisted distal pancreatectomy with celiac axis resection (DP-CAR): A novel minimally invasive approach for achieving adequate dorsal surgical margin

BackgroundDistal pancreatectomy with celiac axis resection (DP-CAR) is a procedure to secure a surgical margin for a locally advanced pancreatic body cancer that invades the celiac axis. However, in patients with cancer close to the root of the celiac axis, obtaining adequate surgical margins can be difficult because the tumor obstructs the field of vision to the root of the celiac axis. Previously, we described the retroperitoneal-first laparoscopic approach (Retlap) to achieve both accurate evaluation of resectability for locally advanced pancreatic cancer requiring DP-CAR [1] and adequate surgical margin for laparoscopic distal pancreatectomy [2]. In this video, we introduce Retlap-assisted DP-CAR as a minimally invasive approach for performing an artery-first pancreatectomy [3, 4] and achieving sufficient dorsal surgical margin (Fig. 1).MethodsOur patient is a 67-year-old man with a 55 × 29-mm pancreatic body tumor after chemotherapy. Preoperative computed tomography revealed a tumor close to the root of the celiac axis. Because the area of tumor invasion on preoperative images was near the root of the celiac artery, Retlap-assisted DP-CAR was performed to determine whether the celiac axis can be secured and obtain an adequate dorsal surgical margin (Fig. 2).ResultsThe operative time and estimated blood loss was 715 min and 449 mL, respectively. In spite of the advanced tumor's location and size, R0 resection was achieved in a minimally invasive way.ConclusionRetlap-assisted DP-CAR is not only technically feasible and useful for achieving accurate evaluation of resectability but also facilitates obtaining an adequate surgical margin.     

Exploiting the tumor-suppressive activity of the androgen receptor by CDK4/6 inhibition in castration-resistant prostate cancer

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La tomographie par émission de positons au 18F-FDG en pathologie rénale non oncologique : indications actuelles et perspectives

Positron emission tomography combined with computed tomography (PET/CT) is a nuclear imaging technique which provides anatomical and functional information. PET/CT is increasingly used in non-oncological nephrology since conventional radiological approaches after injection of contrast agents are relatively contra-indicated in patients with chronic kidney disease (CKD). PET/CT after i.v. injection of ¹⁸F-fluoro-deoxy-glucose (FDG) is not toxic and is characterized by a high sensitivity. The level of irradiation (∼5 mSv) is acceptable. CKD does not significantly influence tissue uptake of ¹⁸F-FDG. The purpose of the present review aims at detailing the non-oncological indications of ¹⁸F-FDG PET/CT in general nephrology and after kidney transplantation. Particularly, ¹⁸F-FDG PET/CT appears useful in the diagnosis of cyst infection in patients with autosomal dominant polycystic kidney disease, as well as in the characterization of retroperitoneal fibrosis. In kidney transplant recipients, ¹⁸F-FDG PET/CT may help in the diagnostic work-up of suspected acute rejection, thereby eventually avoiding unnecessary kidney transplant biopsy. Perspectives in ¹⁸F-FDG PET/CT imaging are discussed, including innovative approaches of image analysis.     

Pulmonary Hypertension in HIV

Human immunodeficiency virus–associated pulmonary arterial hypertension (HIV-PAH) is important to recognize given its association with significant morbidity and mortality. With the introduction of antiretroviral therapy, the focus of disease management has largely shifted from treating immunodeficiency-related opportunistic infections to managing chronic cardiopulmonary complications. Symptoms are nonspecific, and a high index of clinical suspicion is needed to avoid significant delay in the diagnosis of HIV-PAH. Although several viral proteins have been implicated in the pathogenesis of HIV-PAH, the exact mechanism remains uncertain. Further studies are needed to elucidate precise pathogenic mechanisms, early diagnostic tools, and novel therapeutic targets to improve prognosis of this severe complication.