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For intradermal (ID) immunisation, novel needle-based delivery systems have been proposed as a better alternative to the Mantoux method. However, the penetration depth of needles in the human skin and its effect on immune cells residing in the different layers of the skin has not been analyzed. A novel and user-friendly silicon microinjection needle (Bella-mu TM ) has been developed, which allows for a perpendicular injection due to its short needle length (1.4-1.8 mm) and ultrashort bevel. We aimed to characterize the performance of this microinjection needle in the context of the delivery of a particle-based outer membrane vesicle (OMV) vaccine using an ex vivo human skin explant model. We compared the needles of 1.4 and 1.8 mm with the conventional Mantoux method to investigate the depth of vaccine injection and the capacity of the skin antigen-presenting cell (APC) to phagocytose the OMVs. The 1.4 mm needle deposited the antigen closer to the epidermis than the 1.8 mm needle or the Mantoux method. Consequently, activation of epidermal Langerhans cells was significantly higher as determined by dendrite shortening. We found that five different subsets of dermal APCs are able to phagocytose the OMV vaccine, irrespective of the device or injection method. ID delivery using the 1.4 mm needle of a OMV-based vaccine allowed epidermal and dermal APC targeting, with superior activation of Langerhans cells. This study indicates that the use of a microinjection needle improves the delivery of vaccines in the human skin., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

HIV-1 is responsible for a global pandemic of 35 million people and continues to spread at a rate of >2 million new infections/year. It is widely acknowledged that a protective vaccine would be the most effective means to reduce HIV-1 spread and ultimately eliminate the pandemic, whereas a therapeutic vaccine might help to mitigate the clinical course of the disease and to contribute to virus eradication strategies. However, despite more than 30 years of research, we do not have a vaccine capable of protecting against HIV-1 infection or impacting on disease progression. This, in part, denotes the challenge of identifying immunogens and vaccine modalities with a reduced risk of failure in late stage development. However, progress has been made in epitope identification for the induction of broadly neutralizing antibodies. Thus, peptide-based vaccination has become one of the challenges of this decade. While some researchers reconstitute envelope protein conformation and stabilization to conserve the epitope targeted by neutralizing antibodies, others have developed strategies based on peptide-carrier vaccines with a similar goal. Here, we will review the major peptide-carrier based approaches in the vaccine field and their application and recent development in the HIV-1 field., Competing Interests: B.C. and V.V. are members of scientific advisory board of Minka therapeutics.

Pancreas transplantation has now become an established option in the treatment of diabetic complications. It normalizes glucose metabolism, prevents, stabilizes and improves the evolution of diabetes-associated lesions. Improvements in surgical procedure and in immunosuppression have better defined its indications. Combined kidney-pancreas transplantation appears today as the best treatment for the diabetic patient with end stage renal disease. Isolated pancreas transplantation is reserved to non-uremic patients with severe diabetic complications or with hyperlabile glycaemic control and severe impairment of quality of life.

Few data have been published on the course of oxalosis cardiomyopathy after combined liver and kidney transplantation in hyperoxaluria patients with myocardial involvement. We report the case of a primary hyperoxaluria type 1 patient with renal failure who developed end-stage cardiomyopathy. Left venticulography showed severe diffuse hypokinesia and left ventricular ejection fraction was calculated at 12%. Endomyocardial biopsy demonstrated platelike calcium oxalate crystals within the myocardium and the connective tissue, and mild perivascular fibrosis. The patient was first considered for combined liver-heart-kidney transplantation, but as his cardiac function improved slightly with an intensive dialysis program, combined liver and kidney transplantation was performed. Normal cardiac function was demonstrated at 1-year follow-up, and comparative endomyocardial biopsy showed regression of the myocardial oxalate deposits. This case adds stronger clinical, hemodynamic, and histopathological evidence that severe oxalosis cardiomyopathy may be reversed after combined liver and kidney transplantation.

Pancreas transplantation significantly improves the quality of life as well as the survival of the diabetic patient. It is also associated with stabilization and reversal of secondary diabetic complications. Improvements in organ preservation, surgical techniques and immunosuppression have achieved one-year graft survival of more than 90% for combined kidney-pancreas transplant and 80% for isolated pancreas transplantation. Recipient evaluation must weigh the benefits of the procedure with the risk associated with surgery and chronic immunosuppression. Combined kidney-pancreas transplantation appears today as the best treatment for the diabetic patient with end stage renal disease. Isolated pancreas transplantation is reserved to non-uremic patients with severe diabetic complications or with brittle glycaemic control and severe impairment of quality of life.

Bovine serum albumin has been conjugated with kainylaminooxyacetylglycine to afford a multivalent kainylated protein called kainyl-bovine serum albumin (KA-BSA). This derivative, radiolabelled with 125I to more than 5000 Ci/mmol, was found to interact in the chick, goldfish and rat brain to specific membranous sites displaying the pharmacological properties attributed to the kainate sub-type of glutamate receptor. Measurements of the kinetics of association and dissociation of KA-BSA showed a quasi-irreversible binding with dissociation constants in the subpicomolar and nanomolar range. The chemical properties and the binding characteristics of KA-BSA suggest that it interacts mainly with kainate binding sites present in clusters in the membrane. Localization of the KA-BSA binding sites, by autoradiography in the chick cerebellum and by immunoperoxidase staining in the goldfish cerebellum, revealed an exclusive association with the molecular layer.

The kidneys of a patient were removed 3 months after a cadaveric allograft; histological examination revealed tuberculosis and malignant nephroangiosclerosis. When examined one year later, the graft exhibited lesions of glomerulonephritis and of vascular rejection. Immunoglobulin deposits were shown by immunofluorescence in the patient's own kidneys as well as in the graft; they were isolated by acid elution and in both cases had lymphocytotoxic activity in vitro. It is suggested that the target organ released histocompatibility antigen with formation of antigen antibody complexes which deposited in the patient's own kidneys.

Paradoxical embolization of venous thrombus into the abdominal aortic bifurcation has been diagnosed by means of aortography. Lower limb phlebothrombosis accounting for the embolus formation has been demonstrated by phlebography. Arterial embolectomy and venous thrombectomy were successfully performed. Recovery was complete without sequelae.