MVA-based vaccine candidates encoding the native or prefusion-stabilized SARS-CoV-2 spike reveal differential immunogenicity in humans.

In response to the COVID-19 pandemic, multiple vaccines were developed using platforms such as viral vectors and mRNA technology. Here, we report humoral and cellular immunogenicity data from human phase 1 clinical trials investigating two recombinant Modified Vaccinia virus Ankara vaccine candidates, MVA-SARS-2-S and MVA-SARS-2-ST, encoding the native and the prefusion-stabilized SARS-CoV-2 spike protein, respectively. MVA-SARS-2-ST was more immunogenic than MVA-SARS-2-S, but both were less immunogenic compared to licensed mRNA- and ChAd-based vaccines in SARS-CoV-2 naïve individuals. In heterologous vaccination, previous MVA-SARS-2-S vaccination enhanced T cell functionality and MVA-SARS-2-ST boosted the frequency of T cells and S1-specific IgG levels when used as a third vaccination. While the vaccine candidate containing the prefusion-stabilized spike elicited predominantly S1-specific responses, immunity to the candidate with the native spike was skewed towards S2-specific responses. These data demonstrate how the spike antigen conformation, using the same viral vector, directly affects vaccine immunogenicity in humans.

The use of the sodium fluorescein and YELLOW 560 nm filter for the resection of pediatric posterior fossa lesions.

PURPOSE: This study aimed to verify the feasibility, safety, and benefit of using fluorescein sodium (FL) and a YELLOW 560 nm filter in posterior fossa tumors in children. METHODS: All cases of pediatric posterior fossa tumors that have undergone surgery using fluorescein (2018-2022) have been included and were examined retrospectively. In those cases where resection of the tumor was planned, a blinded neuroradiologist distinguished gross total resection and subtotal resection according to the postoperative MRI findings. The surgical report and medical files were reviewed regarding the intraoperative staining grade and adverse events. The grade of fluorescent staining of the targeted lesion was assessed as described in the surgical reports. The screening was conducted for any reference to the degree of fluorescent staining: "intense," "medium," "slight," and "no staining." RESULTS: 19 cases have been included. In 14 cases, a complete resection was initially intended. In 11 of these cases, a gross total resection could be achieved (78.6%). Staining was described as intense in most cases (58.8%). Except for yellow-colored urine, no side effects obviously related to FL were found throughout the observation period. CONCLUSION: In combination with a specific filter, FL is a reliable, safe, and feasible tool in posterior fossa surgery in children.

Persistence of MERS-CoV-spike-specific B cells and antibodies after late third immunization with the MVA-MERS-S vaccine.

The Middle East respiratory syndrome (MERS) is a respiratory disease caused by MERS coronavirus (MERS-CoV). In follow up to a phase 1 trial, we perform a longitudinal analysis of immune responses following immunization with the modified vaccinia virus Ankara (MVA)-based vaccine MVA-MERS-S encoding the MERS-CoV-spike protein. Three homologous immunizations were administered on days 0 and 28 with a late booster vaccination at 12 ± 4 months. Antibody isotypes, subclasses, and neutralization capacity as well as T and B cell responses were monitored over a period of 3 years using standard and bead-based enzyme-linked immunosorbent assay (ELISA), 50% plaque-reduction neutralization test (PRNT50), enzyme-linked immunospot (ELISpot), and flow cytometry. The late booster immunization significantly increases the frequency and persistence of spike-specific B cells, binding immunoglobulin G1 (IgG1) and neutralizing antibodies but not T cell responses. Our data highlight the potential of a late boost to enhance long-term antibody and B cell immunity against MERS-CoV. Our findings on the MVA-MERS-S vaccine may be of relevance for coronavirus 2019 (COVID-19) vaccination strategies.

Increased neutralization and IgG epitope identification after MVA-MERS-S booster vaccination against Middle East respiratory syndrome.

Vaccine development is essential for pandemic preparedness. We previously conducted a Phase 1 clinical trial of the vector vaccine candidate MVA-MERS-S against the Middle East respiratory syndrome coronavirus (MERS-CoV), expressing its full spike glycoprotein (MERS-CoV-S), as a homologous two-dose regimen (Days 0 and 28). Here, we evaluate the safety (primary objective) and immunogenicity (secondary and exploratory objectives: magnitude and characterization of vaccine-induced humoral responses) of a third vaccination with MVA-MERS-S in a subgroup of trial participants one year after primary immunization. MVA-MERS-S booster vaccination is safe and well-tolerated. Both binding and neutralizing anti-MERS-CoV antibody titers increase substantially in all participants and exceed maximum titers observed after primary immunization more than 10-fold. We identify four immunogenic IgG epitopes, located in the receptor-binding domain (RBD, n = 1) and the S2 subunit (n = 3) of MERS-CoV-S. The level of baseline anti-human coronavirus antibody titers does not impact the generation of anti-MERS-CoV antibody responses. Our data support the rationale of a booster vaccination with MVA-MERS-S and encourage further investigation in larger trials. Trial registration: Clinicaltrials.gov NCT03615911.

Decompressive craniectomy and early cranioplasty in a 15-year-old boy with N. meningitidis meningitis.

BACKGROUND: Intracranial hypertension is a well-known life-threatening complication of bacterial meningitis. Investigations on decompressive craniectomy after failure of conservative management are scarce, but this surgical treatment should be considered and performed expeditiously, as it lowers the intracranial pressure and improves brain tissue oxygenation. Early cranioplasty can further aid the rehabilitation. CASE DESCRIPTION: A 15-year-old boy was admitted to our emergency department because of sudden onset of neurologic decline and consecutive loss of consciousness. Clinical examination and imaging showed elevated intracranial pressure, leading to the suspected diagnosis of meningitis. Intracranial pressure monitoring was installed, but the initiated conservative management failed. Finally, the patient underwent bilateral decompressive craniectomy. The microbiological test showed growth of Neisseria meningitidis. After full neurologic recovery, cranioplasty with two CAD/CAM titanium implants was conducted successfully. CONCLUSIONS: This unique report shows that decompressive craniotomy with duroplasty may be a crucial therapeutic approach in bacterial meningitis with refractory increased intracranial pressure and brainstem compression. Early cranioplasty with a patient-specific implant allowed the early and full reintegration of the patient.

Use of intrathecal baclofen in children and adolescents: interdisciplinary consensus table 2013.

In recent years, intrathecal baclofen (ITB) has attained an important role in the treatment of severe spasticity and dystonia in children. There are principal differences between the use of ITB in children and its use in neurology and oncology in adults. Here, we present a consensus report on best practice for the treatment of severe spastic and dystonic movement disorders with ITB. Using a problem-orientated approach to integrate theories and methods, the consensus was developed by an interdisciplinary group of experienced ITB users and experts in the field of movement disorders involving 14 German centers. On the basis of the data pooled from more than 400 patients, the authors have summarized their experience and supporting evidence in tabular form to provide a concise, but still a comprehensive information base that represents our current understanding regarding ITB treatment options in children and adolescents.

Fatal hemorrhagic stroke in a Caucasian girl with moyamoya disease.

INTRODUCTION: Moyamoya disease (MMD) is an extremely rare neurovascular disorder in Caucasian children. To the best of our knowledge, the aggressive variant including hemorrhagic malignant stroke and consecutive global ischemia has not been reported for this population before. CASE REPORT: We present the case of an 11-year-old girl with sudden neurological deterioration due to intracerebral hemorrhage with early irruption into the ventricular system. MMD with extensive neovascularization was diagnosed by means of computed tomography and magnetic resonance imaging. Despite immediate ventricular drainage, intracranial pressure increased above the mean arterial pressure resulting in malignant bi-hemispheric ischemia. The girl died within 53 h after admission to hospital. DISCUSSION: Intracerebral hemorrhage in young patients is often attributed to vascular malformation. This case shows that MMD may constitute a potential diagnosis in the case of sudden neurological deterioration and loss of consciousness, even in previously healthy children.

The influence of violent and nonviolent computer games on implicit measures of aggressiveness.

We examined the causal relationship between playing violent video games and increases in aggressiveness by using implicit measures of aggressiveness, which have become important for accurately predicting impulsive behavioral tendencies. Ninety-six adults were randomly assigned to play one of three versions of a computer game that differed only with regard to game content (violent, peaceful, or abstract game), or to work on a reading task. In the games the environmental context, mouse gestures, and physiological arousal-as indicated by heart rate and skin conductance-were kept constant. In the violent game soldiers had to be shot, in the peaceful game sunflowers had to be watered, and the abstract game simply required clicking colored triangles. Five minutes of play did not alter trait aggressiveness, yet an Implicit Association Test detected a change in implicit aggressive self-concept. Playing a violent game produced a significant increase in implicit aggressive self-concept relative to playing a peaceful game. The well-controlled study closes a gap in the research on the causality of the link between violence exposure in computer games and aggressiveness with specific regard to implicit measures. We discuss the significance of importing recent social-cognitive theory into aggression research and stress the need for further development of aggression-related implicit measures.

Countertransference reactions in therapeutic work with incestuous sexual abusers.

The study was a qualitative investigation aimed at therapists' responses to working with a population of incestuous sexual abusers. Semi-structured interviews were conducted with nine therapists who were recruited from psychotherapy, psychology, and forensic psychology services in the National Health Service (NHS) in the UK. The predominant therapeutic model was psychodynamic; however, cognitive-behavioural and integrative approaches were practiced by some therapists. The data were analyzed using interpretative phenomenological analysis (Smith, 1996). Results suggested that the therapists experienced a considerable amount of negative and difficult feelings and that they tended to experience feeling controlled and deceived, which seemed to influence their ability to create and maintain the therapeutic relationship. It was suggested that the dynamics of incestuous sexual abuse played a part in these difficulties. The results are discussed with reference to the clinical therapeutic literature.

[On the effect of mutations of the fibroblast growth factor receptors as exemplified by three cases of craniosynostoses]. / Uber die Wirkung von Mutationen der Fibroblastenwachstumsfaktorrezeptoren (FGFR) am Beispiel dreier Fälle mit Kraniosynostosen.

PURPOSE: Craniosynostoses are premature ossifications of cranial sutures. They occur isolated and syndromic. Syndromic craniosynostoses are mainly associated with mutations of the Fibroblast Growth Factor Receptors (FGFR) 1 - 3. This paper gives an overview of the etiology and pathophysiology of isolated and syndromic craniosynostoses and discusses the molecular genetic results in 21 index cases (19 seemingly isolated craniosynostoses, 2 cases with a clinical diagnosis of Crouzon's syndrome). METHOD: Mutation analysis in exons of the FGFR 1 - 3 known to be preferentially affected in craniosynostoses was performed on DNA samples from peripheral blood and bone specimen excised at the time of surgery to correct the craniosynostosis. RESULTS: In a girl with seemingly isolated plagiocephaly we identified a P250L (749C-->T) mutation in FGFR3. Her mother showed minor signs of craniosynostosis when the family was re-evaluated. She was shown to carry the same mutation. In two patients with suspected Crouzon's syndrome 2 different mutations were detected at the same nucleotide (1025G-->A or C) and confirmed the clinical diagnosis. No mutation was found in 18/19 seemingly isolated craniosynostosis cases. CONCLUSION: In contrast to syndromic forms isolated craniosynostoses are rarely associated with mutations in FGFR. The affection of further family members is a strong indication of involvement of FGFR mutations. Because of variable expressivity, parents should be examined carefully in isolated craniosynostoses to identify minor signs.