Enhancing Immunogenicity of a Thermostable, Efficacious SARS-CoV-2 Vaccine Formulation through Oligomerization and Adjuvant Choice.

Currently deployed SARS-CoV-2 vaccines all require storage at refrigerated or sub-zero temperatures. We demonstrate that after month-long incubation at 37 °C, solubilization, and formulation with squalene-in-water emulsion adjuvant, a stabilized receptor binding domain retains immunogenicity and protective efficacy. We also examine the effects of trimerization of the stabilized RBD, as well as of additional adjuvants, on both B and T-cell responses.

Enhanced protective efficacy of a thermostable RBD-S2 vaccine formulation against SARS-CoV-2 and its variants.

With the rapid emergence of variants of concern (VOC), the efficacy of currently licensed vaccines has reduced drastically. VOC mutations largely occur in the S1 subunit of Spike. The S2 subunit of SARS-CoV-2 is conserved and thus more likely to elicit broadly reactive immune responses that could improve protection.

Decreasing Time Intervals in Recurring Capsular Contracture? A Single Center Retrospective Study over 6 Years.

Unlabelled: Although breast implants of the current generation can, in principle, remain in the body for life, follow-up operations of the augmented or reconstructed breasts are regularly necessary. Capsular contracture is the leading cause for revisional surgery. The aim of this study was to evaluate indications and changes in time intervals between consecutive implant replacements with a focus on capsular contracture.

Characterization and comparison of novel adjuvants for a prefusion clamped MERS vaccine.

Various chemical adjuvants are available to augment immune responses to non-replicative, subunit vaccines. Optimized adjuvant selection can ensure that vaccine-induced immune responses protect against the diversity of pathogen-associated infection routes, mechanisms of infectious spread, and pathways of immune evasion. In this study, we compare the immune response of mice to a subunit vaccine of Middle Eastern respiratory syndrome coronavirus (MERS-CoV) spike protein, stabilized in its prefusion conformation by a proprietary molecular clamp (MERS SClamp) alone or formulated with one of six adjuvants: either () aluminium hydroxide, () SWE, a squalene-in-water emulsion, () SQ, a squalene-in-water emulsion containing QS21 saponin, () SMQ, a squalene-in-water emulsion containing QS21 and a synthetic toll-like receptor 4 (TLR4) agonist 3D-6-acyl Phosphorylated HexaAcyl Disaccharide (3D6AP); () LQ, neutral liposomes containing cholesterol, 1.

Phage display-based discovery of cyclic peptides against the broad spectrum bacterial anti-virulence target CsrA.

Small macrocyclic peptides are promising candidates for new anti-infective drugs. To date, such peptides have been poorly studied in the context of anti-virulence targets. Using phage display and a self-designed peptide library, we identified a cyclic heptapeptide that can bind the carbon storage regulator A (CsrA) from Yersinia pseudotuberculosis and displace bound RNA.

Validation of a Sensor-Based Gait Analysis System with a Gold-Standard Motion Capture System in Patients with Parkinson's Disease.

Digital technologies provide the opportunity to analyze gait patterns in patients with Parkinson's Disease using wearable sensors in clinical settings and a home environment. Confirming the technical validity of inertial sensors with a 3D motion capture system is a necessary step for the clinical application of sensor-based gait analysis. Therefore, the objective of this study was to compare gait parameters measured by a mobile sensor-based gait analysis system and a motion capture system as the gold standard.

Development of molecular clamp stabilized hemagglutinin vaccines for Influenza A viruses.

Influenza viruses cause a significant number of infections and deaths annually. In addition to seasonal infections, the risk of an influenza virus pandemic emerging is extremely high owing to the large reservoir of diverse influenza viruses found in animals and the co-circulation of many influenza subtypes which can reassort into novel strains. Development of a universal influenza vaccine has proven extremely challenging.

The Immunogenicity of Capsid-Like Particle Vaccines in Combination with Different Adjuvants Using Different Routes of Administration.

Capsid-like particle (CLP) displays can be used to enhance the immunogenicity of vaccine antigens, but a better understanding of how CLP vaccines are best formulated and delivered is needed. This study compared the humoral immune responses in mice elicited against two different vaccine antigens (a bacterial protein and a viral peptide) delivered on an AP205 CLP platform using six different adjuvant formulations. In comparison to antibody responses obtained after immunization with the unadjuvanted CLP vaccine, three of the adjuvant systems (neutral liposomes/monophosphoryl lipid A/quillaja saponaria 21, squalene-in-water emulsion, and monophosphoryl lipid A) caused significantly increased antibody levels, whereas formulation with the three other adjuvants (aluminum hydroxide, cationic liposomes, and cationic microparticles) resulted in similar or even decreased antibody responses.

Antibiotic treatment and prophylaxis of periprosthetic infections: Evaluation of 666 consecutive breast implant removals.

Periprosthetic infections are feared complications in esthetic and reconstructive breast surgery. The purpose of our study is to evaluate our institution's specific culture data and to identify most common organisms and suitable antibiotics for prophylaxis and first-line treatment. We evaluated all patients with a change or removal of breast implants from 01.

Hit-to-lead optimization of a latency-associated nuclear antigen inhibitor against Kaposi's sarcoma-associated herpesvirus infections.

The Latency-associated nuclear antigen (LANA) plays a central role for the latent persistence of the Kaposi's Sarcoma Herpesvirus (KSHV) in the human host and helps to establish lifelong infections. Herein, we report our efforts towards hit-to-lead generation starting from a previously discovered LANA-DNA inhibitor. By tethering the viral genome to the host nucleosomes, LANA ensures the segregation and persistence of the viral DNA during mitosis.

Discovery of Novel Latency-Associated Nuclear Antigen Inhibitors as Antiviral Agents Against Kaposi's Sarcoma-Associated Herpesvirus.

With the aim to develop novel antiviral agents against Kaposi's Sarcoma Herpesvirus (KSHV), we are targeting the latency-associated nuclear antigen (LANA). This protein plays an important role in viral genome maintenance during latent infection. LANA has the ability to tether the viral genome to the host nucleosomes and, thus, ensures latent persistence of the viral genome in the host cells.

Efficacy of three innovative bacterin vaccines against experimental infection with Mycoplasma hyopneumoniae.

New vaccine formulations that include novel strains of Mycoplasma hyopneumoniae and innovative adjuvants designed to induce cellular immunity could improve vaccine efficacy against this pathogen. The aim of this experimental study was to assess the efficacy of three experimental bacterin formulations based on M. hyopneumoniae field strain F7.

Restriction-Free Construction of a Phage-Presented Very Short Macrocyclic Peptide Library.

Phage display is a commonly used technology for the screening of large clonal libraries of proteins and peptides. The construction of peptide libraries containing very short sequences, however, poses certain problems for conventional restriction-based cloning procedures, which are rooted in the necessity to purify restricted library oligos. Herein, we present an alternative cloning method especially suitable for such very short sequences of about only 21 base pairs resulting in a 60 bp insert.

Electroporation of a nanoparticle-associated DNA vaccine induces higher inflammation and immunity compared to its delivery with microneedle patches in pigs.

DNA vaccination is an attractive technology, based on its well-established manufacturing process, safety profile, adaptability to rapidly combat pandemic pathogens, and stability at ambient temperature; however an optimal delivery method of DNA remains to be determined. As pigs are a relevant model for humans, we comparatively evaluated the efficiency of vaccine DNA delivery in vivo to pigs using dissolvable microneedle patches, intradermal inoculation with needle (ID), surface electroporation (EP), with DNA associated or not to cationic poly-lactic-co-glycolic acid nanoparticles (NPs). We used a luciferase encoding plasmid (pLuc) as a reporter and vaccine plasmids encoding antigens from the Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), a clinically-significant swine arterivirus.

A DNA-Modified Live Vaccine Prime-Boost Strategy Broadens the T-Cell Response and Enhances the Antibody Response against the Porcine Reproductive and Respiratory Syndrome Virus.

The Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) induces reproductive disorders in sows and respiratory illnesses in growing pigs and is considered as one of the main pathogenic agents responsible for economic losses in the porcine industry worldwide. Modified live PRRSV vaccines (MLVs) are very effective vaccine types against homologous strains but they present only partial protection against heterologous viral variants. With the goal to induce broad and cross-protective immunity, we generated DNA vaccines encoding B and T antigens derived from a European subtype 1 strain that include T-cell epitope sequences known to be conserved across strains.

Systems Immunology Characterization of Novel Vaccine Formulations for Bacterins.

We characterized five different vaccine candidates and a commercial vaccine in terms of safety, immunogenicity and using a systems vaccinology approach, with the aim to select novel vaccine candidates against . Seven groups of six -free piglets were primo- and booster vaccinated with the different experimental bacterin formulations, the commercial vaccine Hyogen® as a positive control or PBS as a negative control. The experimental bacterin was formulated with cationic liposomes + c-di-AMP (Lipo_AMP), cationic liposomes + Toll-like receptor (TLR) 2/1, TLR7, and TLR9 ligands (TLR ligands; Lipo_TLR), micro-particles + TLR ligands (PLGA_TLR), squalene-in-water emulsion + TLR ligands (SWE_TLR), or DDA:TDB liposomes (Lipo_DDA:TDB).

Fragment-Based Discovery of a Qualified Hit Targeting the Latency-Associated Nuclear Antigen of the Oncogenic Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8.

The latency-associated nuclear antigen (LANA) is required for latent replication and persistence of Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8. It acts via replicating and tethering the virus episome to the host chromatin and exerts other functions. We conceived a new approach for the discovery of antiviral drugs to inhibit the interaction between LANA and the viral genome.

Apd1 and Aim32 Are Prototypes of Bishistidinyl-Coordinated Non-Rieske [2Fe-2S] Proteins.

Apd1, a cytosolic yeast protein, and Aim32, its counterpart in the mitochondrial matrix, have a C-terminal thioredoxin-like ferredoxin (TLF) domain and a widely divergent N-terminal domain. These proteins are found in bacteria, plants, fungi, and unicellular pathogenic eukaryotes but not in Metazoa. Our chemogenetic experiments demonstrate that the highly conserved cysteine and histidine residues within the C-X-C-X-H-X-G-G-H motif of the TLF domain of Apd1 and Aim32 proteins are essential for viability of yeast cells upon treatment with the redox mediators gallobenzophenone or pyrogallol, respectively.

[Evaluation of the infrastructure for clinical surgical studies in Germany : A nationwide survey of the surgical study network CHIR-Net].

Background: In order to improve the quality and quantity of clinical trials in Germany a surgical study network called CHIR-Net funded by the Federal Ministry of Education and Research (BMBF) was established. The focus was on building an infrastructure for the performance of surgical multicenter, randomized controlled clinical trials with the inclusion of university and non-university hospitals. The education of clinicians with an interest in clinical research and the transfer of research ideas (as investigator initiated trials, IIT) were clear goals for this grant.

Accounting for adjuvant-induced artifacts in the characterization of vaccine formulations by polyacrylamide gel electrophoresis.

Objectives: Several vaccine adjuvants comprise complex nano- or micro-particle formulations, such as oil-in-water emulsions. In order to characterize interactions and compatibility of oil-in-water emulsion adjuvants with protein antigens in vaccines, effective protein characterization methods that can accommodate potential interference from high concentrations of lipid-based particles are needed.

Methods: Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) is a standard protein characterization technique which is affected by the presence of adjuvants such as oil-in-water emulsions.

[Assessment of the benefit of medical devices in surgical practice. Problems and possible solutions].

The market approval of medical devices in Germany does not yet require a benefit assessment. Thus, there is a lack of high quality studies that clearly prove the benefit of medical innovations. In the past, the Federal Joint Committee in Germany (G-BA) did not have the opportunity to adequately address this issue of lacking evidence.

[Rotating physician in CHIR-Net. Evaluation of the curriculum].

Background: Conduction of and participation in clinical trials is a major challenge for surgical departments especially as job performance in hospitals has increased immensely during the last few years due to economic aspects. Only 11.7 % of published clinical studies are randomized controlled trials.

[Why nurses fly and surgeons rotate. The surgical study network CHIR-Net].

Background: The German National Surgical Trial Network (CHIR-Net) which has been funded since 2006 by the Federal Ministry of Education and Research (BMBF, funding code 01GH1001A-01GH1001F, 01GH0702) is made up of eight regional surgical centers. The aim of the CHIR-Net is the design, implementation and publication of prospective, randomized, multicenter trials to support evidence-based medicine in surgery. Two main pillars of the CHIR-Net are the surgeon on rotation program and the flying study nurse program.