An Adjuvanted Vaccine-Induced Pathogenesis Following Influenza Virus Infection.

An incomplete Freund's adjuvant elicited an overt pathogenesis in vaccinated mice following the intranasal challenge of A/California/07/2009 (H1N1) virus despite the induction of a higher specific antibody titer than other adjuvanted formulations. Aluminum hydroxide adjuvants have not induced any pathogenic signs in a variety of formulations with glycolipids. A glycolipid, α-galactosyl ceramide, improved a stimulatory effect of distinct adjuvanted formulations on an anti-influenza A antibody response.

The presence of broadly neutralizing anti-SARS-CoV-2 RBD antibodies elicited by primary series and booster dose of COVID-19 vaccine.

Antibody-mediated immunity plays a key role in protection against SARS-CoV-2. We characterized B-cell-derived anti-SARS-CoV-2 RBD antibody repertoires from vaccinated and infected individuals and elucidate the mechanism of action of broadly neutralizing antibodies and dissect antibodies at the epitope level. The breadth and clonality of anti-RBD B cell response varies among individuals.

Current understanding of the molecular mechanisms of chemotherapy-induced peripheral neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is the most common off-target adverse effects caused by various chemotherapeutic agents, such as cisplatin, oxaliplatin, paclitaxel, vincristine and bortezomib. CIPN is characterized by a substantial loss of primary afferent sensory axonal fibers leading to sensory disturbances in patients. An estimated of 19-85% of patients developed CIPN during the course of chemotherapy.

Real-time field-programmable gate array-based closed-loop deep brain stimulation platform targeting cerebellar circuitry rescues motor deficits in a mouse model of cerebellar ataxia.

Aims: The open-loop nature of conventional deep brain stimulation (DBS) produces continuous and excessive stimulation to patients which contributes largely to increased prevalence of adverse side effects. Cerebellar ataxia is characterized by abnormal Purkinje cells (PCs) dendritic arborization, loss of PCs and motor coordination, and muscle weakness with no effective treatment. We aim to develop a real-time field-programmable gate array (FPGA) prototype targeting the deep cerebellar nuclei (DCN) to close the loop for ataxia using conditional double knockout mice with deletion of PC-specific LIM homeobox (Lhx)1 and Lhx5, resulting in abnormal dendritic arborization and motor deficits.

Genome-wide study reveals novel roles for formin-2 in axon regeneration as a microtubule dynamics regulator and therapeutic target for nerve repair.

Peripheral nerves regenerate successfully; however, clinical outcome after injury is poor. We demonstrated that low-dose ionizing radiation (LDIR) promoted axon regeneration and function recovery after peripheral nerve injury (PNI). Genome-wide CpG methylation profiling identified LDIR-induced hypermethylation of the Fmn2 promoter, exhibiting injury-induced Fmn2 downregulation in dorsal root ganglia (DRGs).

Low-dose ionizing radiation promotes motor recovery and brain rewiring by resolving inflammatory response after brain injury and stroke.

Traumatic brain injury (TBI) and stroke share a common pathophysiology that worsens over time due to secondary tissue injury caused by sustained inflammatory response. However, studies on pharmacological interventions targeting the complex secondary injury cascade have failed to show efficacy. Here, we demonstrated that low-dose ionizing radiation (LDIR) reduced lesion size and reversed motor deficits after TBI and photothrombotic stroke.

Pilot-scale production of inactivated monoglycosylated split HN influenza virus vaccine provides cross-strain protection against influenza viruses.

Influenza epidemics and pandemics caused by newly emerging virus strains highlight an urgent need to develop a universal vaccine against viruses. Previously, a monoglycosylated X-181 vaccine demonstrated that the HA possessing a single N-acetylglucosamine at each N-glycosylation site is superior to confer broader protection in mice than conventional vaccines. However, the greatest challenge in conducting clinical trials is the need to develop robust manufacturing processes capable of producing vaccines at the pilot scale with the desired stability, potency, and efficacy.

Toward a cerebello-thalamo-cortical computational model of spinocerebellar ataxia.

Computational neural network modelling is an emerging approach for optimization of drug treatment of neurological disorders and fine-tuning of rehabilitation strategies. In the current study, we constructed a cerebello-thalamo-cortical computational neural network model to simulate a mouse model of cerebellar ataxia (pcd mice) by manipulating cerebellar bursts through reduction of GABAergic inhibitory input. Cerebellar output neurons were projected to the thalamus and bidirectionally connected with the cortical network.

Structure of the heterotrimeric membrane protein complex FtsB-FtsL-FtsQ of the bacterial divisome.

The synthesis of the cell-wall peptidoglycan during bacterial cell division is mediated by a multiprotein machine, called the divisome. The essential membrane protein complex of FtsB, FtsL and FtsQ (FtsBLQ) is at the heart of the divisome assembly cascade in Escherichia coli. This complex regulates the transglycosylation and transpeptidation activities of the FtsW-FtsI complex and PBP1b via coordination with FtsN, the trigger for the onset of constriction.

Structural basis for a conserved neutralization epitope on the receptor-binding domain of SARS-CoV-2.

Antibody-mediated immunity plays a crucial role in protection against SARS-CoV-2 infection. We isolated a panel of neutralizing anti-receptor-binding domain (RBD) antibodies elicited upon natural infection and vaccination and showed that they recognize an immunogenic patch on the internal surface of the core RBD, which faces inwards and is hidden in the "down" state. These antibodies broadly neutralize wild type (Wuhan-Hu-1) SARS-CoV-2, Beta and Delta variants and some are effective against other sarbecoviruses.

A small molecule M1 promotes optic nerve regeneration to restore target-specific neural activity and visual function.

Axon regeneration is an energy-demanding process that requires active mitochondrial transport. In contrast to the central nervous system (CNS), axonal mitochondrial transport in regenerating axons of the peripheral nervous system (PNS) increases within hours and sustains for weeks after injury. Yet, little is known about targeting mitochondria in nervous system repair.

Structural basis of interleukin-17B receptor in complex with a neutralizing antibody for guiding humanization and affinity maturation.

Upregulation of interleukin-17 receptor B (IL-17RB) is known to be oncogenic, while other IL-17 receptors and ligands are generally involved in pro-inflammatory pathways. We identify a mouse neutralizing monoclonal antibody (mAb) D9, which blocks the IL-17RB/IL-17B pathway and inhibits pancreatic tumorigenesis in an orthotopic mouse model. The X-ray crystal structure of the IL-17RB ectodomain in complex with its neutralizing antibody D9 shows that D9 binds to a predicted ligand binding interface and engages with the A'-A loop of IL-17RB fibronectin III domain 1 in a unique conformational state.

Clinically relevant small-molecule promotes nerve repair and visual function recovery.

Adult mammalian injured axons regenerate over short-distance in the peripheral nervous system (PNS) while the axons in the central nervous system (CNS) are unable to regrow after injury. Here, we demonstrated that Lycium barbarum polysaccharides (LBP), purified from Wolfberry, accelerated long-distance axon regeneration after severe peripheral nerve injury (PNI) and optic nerve crush (ONC). LBP not only promoted intrinsic growth capacity of injured neurons and function recovery after severe PNI, but also induced robust retinal ganglion cell (RGC) survival and axon regeneration after ONC.

Cerebellar glutamatergic system impacts spontaneous motor recovery by regulating Gria1 expression.

Peripheral nerve injury (PNI) often results in spontaneous motor recovery; however, how disrupted cerebellar circuitry affects PNI-associated motor recovery is unknown. Here, we demonstrated disrupted cerebellar circuitry and poor motor recovery in ataxia mice after PNI. This effect was mimicked by deep cerebellar nuclei (DCN) lesion, but not by damaging non-motor area hippocampus.

Debulking different Corona (SARS-CoV-2 delta, omicron, OC43) and Influenza (H1N1, H3N2) virus strains by plant viral trap proteins in chewing gums to decrease infection and transmission.

Because oral transmission of SARS-CoV-2 is 3-5 orders of magnitude higher than nasal transmission, we investigated debulking of oral viruses using viral trap proteins (CTB-ACE2, FRIL) expressed in plant cells, delivered through the chewing gum. In omicron nasopharyngeal (NP) samples, the microbubble count (based on N-antigen) was significantly reduced by 20 μg of FRIL (p < 0.0001) and 0.

Guillain-Barré syndrome in children - High occurrence of Miller Fisher syndrome in East Asian region.

Background: Guillain-Barré syndrome (GBS) is a rare acquired immune-mediated polyneuropathy. Updated population-based data concerning paediatric GBS is needed.

Methods: Paediatric patients aged below 18 years diagnosed with GBS between 2009 and 2018 in all 11 paediatric departments in Hong Kong were identified from the Hong Kong Hospital Authority Clinical Data Analysis and Reporting System.

Functional and Phenotypic Diversity of Microglia: Implication for Microglia-Based Therapies for Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and is closely associated with the accumulation of β-amyloid (Aβ) and neurofibrillary tangles (NFTs). Apart from Aβ and NFT pathologies, AD patients also exhibit a widespread microglial activation in various brain regions with elevated production of pro-inflammatory cytokines, a phenomenon known as neuroinflammation. In healthy central nervous system, microglia adopt ramified, "surveying" phenotype with compact cell bodies and elongated processes.

Deep Brain Stimulation of the Interposed Nucleus Reverses Motor Deficits and Stimulates Production of Anti-inflammatory Cytokines in Ataxia Mice.

Cerebellum is one of the major targets of autoimmunity and cerebellar damage that leads to ataxia characterized by the loss of fine motor coordination and balance, with no treatment available. Deep brain stimulation (DBS) could be a promising treatment for ataxia but has not been extensively investigated. Here, our study aims to investigate the use of interposed nucleus of deep cerebellar nuclei (IN-DCN) for ataxia.

Neuroinflammation, Microglia and Implications for Retinal Ganglion Cell Survival and Axon Regeneration in Traumatic Optic Neuropathy.

Traumatic optic neuropathy (TON) refers to a pathological condition caused by a direct or indirect insult to the optic nerves, which often leads to a partial or permanent vision deficit due to the massive loss of retinal ganglion cells (RGCs) and their axonal fibers. Retinal microglia are immune-competent cells residing in the retina. In rodent models of optic nerve crush (ONC) injury, resident retinal microglia gradually become activated, form end-to-end alignments in the vicinity of degenerating RGC axons, and actively internalized them.

Vaccination with SARS-CoV-2 spike protein lacking glycan shields elicits enhanced protective responses in animal models.

A major challenge to end the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to develop a broadly protective vaccine that elicits long-term immunity. As the key immunogen, the viral surface spike (S) protein is frequently mutated, and conserved epitopes are shielded by glycans. Here, we revealed that S protein glycosylation has site-differential effects on viral infectivity.

Active Humoral Response Reverts Tumorigenicity through Disruption of Key Signaling Pathway.

Immune checkpoint inhibitors such as monoclonal antibodies (mAbs) are amongst the most important breakthroughs in cancer therapeutics. However, high cost and short acting time limits its affordability and clinical application. Therefore, an economical and durable alternative is urgently needed.

Glycosite-deleted mRNA of SARS-CoV-2 spike protein as a broad-spectrum vaccine.

Development of the messenger RNA (mRNA) vaccine has emerged as an effective and speedy strategy to control the spread of new pathogens. After vaccination, the mRNA is translated into the real protein vaccine, and there is no need to manufacture the protein in vitro. However, the fate of mRNA and its posttranslational modification inside the cell may affect immune response.

Structures and therapeutic potential of anti-RBD human monoclonal antibodies against SARS-CoV-2.

Administration of potent anti-receptor-binding domain (RBD) monoclonal antibodies has been shown to curtail viral shedding and reduce hospitalization in patients with SARS-CoV-2 infection. However, the structure-function analysis of potent human anti-RBD monoclonal antibodies and its links to the formulation of antibody cocktails remains largely elusive. Previously, we isolated a panel of neutralizing anti-RBD monoclonal antibodies from convalescent patients and showed their neutralization efficacy .

Correction: Breadth and function of antibody response to acute SARS-CoV-2 infection in humans.

[This corrects the article DOI: 10.1371/journal.ppat.

Vaccinia virus-based vaccines confer protective immunity against SARS-CoV-2 virus in Syrian hamsters.

COVID-19 in humans is caused by Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that belongs to the beta family of coronaviruses. SARS-CoV-2 causes severe respiratory illness in 10-15% of infected individuals and mortality in 2-3%. Vaccines are urgently needed to prevent infection and to contain viral spread.