Hybrid immunity augments cross-variant protection against COVID-19 among immunocompromised individuals.

Background: Immunity to SARS-CoV-2 vaccination and infection differs considerably among individuals. We investigate the critical pathways that influence vaccine-induced cross-variant serological immunity among individuals at high-risk of COVID-19 complications.

Methods: Neutralizing antibodies to the wild-type SARS-CoV-2 virus and its variants (Beta, Gamma, Delta and Omicron) were analyzed in patients with autoimmune diseases, chronic comorbidities (multimorbidity), and healthy controls.

Single-shot dendritic cell targeting SARS-CoV-2 vaccine candidate induces broad, durable and protective systemic and mucosal immunity in mice.

Current coronavirus disease 2019 vaccines face limitations including waning immunity, immune escape by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, limited cellular response, and poor mucosal immunity. We engineered a Clec9A-receptor binding domain (RBD) antibody construct that delivers the SARS-CoV-2 RBD to conventional type 1 dendritic cells. Compared with non-targeting approaches, single dose immunization in mice with Clec9A-RBD induced far higher RBD-specific antibody titers that were sustained for up to 21 months after vaccination.

SNR of a combined mode-locked fiber laser generating conventional and dissipative solitons.

In this paper, we utilized a combined mode-locked fiber laser including a saturable absorber mirror (SESAM) and nonlinear polarization evolution (NPE) to generate conventional solitons (CSs) and dissipative solitons (DSs), respectively, in order to investigate the difference in signal-to-noise ratio (SNR) between the outputs of these two types of solitons in artificial and natural saturators. Both simulation and experimental results demonstrated that, under the shared pump power, the DSs from the NPE-based mode-locked fiber output exhibited a higher SNR of approximately 60 dB, compared to the CSs from the SESAM-based mode-locked fiber output of 45 dB. Furthermore, we conducted theoretical analysis of these results.

Durable cross-protective neutralizing antibody responses elicited by lipid nanoparticle-formulated SARS-CoV-2 mRNA vaccines.

The advent of SARS-CoV-2 variants with defined mutations that augment pathogenicity and/or increase immune evasiveness continues to stimulate global efforts to improve vaccine formulation and efficacy. The extraordinary advantages of lipid nanoparticles (LNPs), including versatile design, scalability, and reproducibility, make them ideal candidates for developing next-generation mRNA vaccines against circulating SARS-CoV-2 variants. Here, we assess the efficacy of LNP-encapsulated mRNA booster vaccines encoding the spike protein of SARS-CoV-2 for variants of concern (Delta, Omicron) and using a predecessor (YN2016C isolated from bats) strain spike protein to elicit durable cross-protective neutralizing antibody responses.

Relative deficiency in interferon-γ-secreting CD4+ T cells is strongly associated with poorer COVID-19 vaccination responses in older adults.

Although the two-dose mRNA vaccination regime provides protection against SARS-CoV-2, older adults have been shown to exhibit poorer vaccination responses. In addition, the role of vaccine-induced T-cell responses is not well characterised. We aim to assess the impact of age on immune responses after two doses of the BNT162b2 mRNA vaccine, focussing on antigen-specific T-cells.

Employment of a high throughput functional assay to define the critical factors that influence vaccine induced cross-variant neutralizing antibodies for SARS-CoV-2.

The scale and duration of neutralizing antibody responses targeting SARS-CoV-2 viral variants represents a critically important serological parameter that predicts protective immunity for COVID-19. In this study, we describe the development and employment of a new functional assay that measures neutralizing antibodies for SARS-CoV-2 and present longitudinal data illustrating the impact of age, sex and comorbidities on the kinetics and strength of vaccine-induced antibody responses for key variants in an Asian volunteer cohort. We also present an accurate quantitation of serological responses for SARS-CoV-2 that exploits a unique set of in-house, recombinant human monoclonal antibodies targeting the viral Spike and nucleocapsid proteins and demonstrate a reduction in neutralizing antibody titres across all groups 6 months post-vaccination.

SHEAR saliva collection device augments sample properties for improved analytical performance.

Despite being a convenient clinical substrate for biomonitoring, saliva's widespread utilization has not yet been realized. The non-Newtonian, heterogenous, and highly viscous nature of saliva complicate the development of automated fluid handling processes that are vital for accurate diagnoses. Furthermore, conventional saliva processing methods are resource and/or time intensive precluding certain testing capabilities, with these challenges aggravated during a pandemic.

Defining neutralization and allostery by antibodies against COVID-19 variants.

The changing landscape of SARS-CoV-2 Spike protein is linked to the emergence of variants, immune-escape and reduced efficacy of the existing repertoire of anti-viral antibodies. The functional activity of neutralizing antibodies is linked to their quaternary changes occurring as a result of antibody-Spike trimer interactions. Here, we reveal the conformational dynamics and allosteric perturbations linked to binding of novel human antibodies and the viral Spike protein.

Analyzing COVID-19 Vaccine Responses in Transplant Recipients.

COVID-19 vaccination has significantly impacted the global pandemic by reducing the severity of infection, lowering rates of hospitalization, and reducing morbidity/mortality in healthy individuals. However, the degree of vaccine-induced protection afforded to renal transplant recipients who receive forms of maintenance immunosuppression remains poorly defined. This is particularly important when we factor in the emergence of SARS-CoV-2 variants of concern (VOCs) that have defined mutations that reduce the effectiveness of Ab responses targeting the Spike Ags from the ancestral Wuhan-Hu-1 variants employed in the most widely used vaccine formats.

Switching Heavy Chain Constant Domains Denatures the Paratope 3D Architecture of Influenza Monoclonal Antibodies.

Several human monoclonal Abs for treating Influenza have been evaluated in clinical trials with limited success despite demonstrating superiority in preclinical animal models including mice. To conduct efficacy studies in mice, human monoclonal Abs are genetically engineered to contain mouse heavy chain constant domain to facilitate the engagement of Fc-receptors on mouse immune effector cells. Although studies have consistently reported discrepancies in Ab effectiveness following genetic engineering, the structural and mechanistic basis for these inconsistencies remain uncharacterized.

Efficient recall of SARS-CoV-2 variant-reactive B cells and T responses in the elderly upon heterologous mRNA vaccines as boosters.

Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID-19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited.

A rapid simple point-of-care assay for the detection of SARS-CoV-2 neutralizing antibodies.

Background: Neutralizing antibodies (NAbs) prevent pathogens from infecting host cells. Detection of SARS-CoV-2 NAbs is critical to evaluate herd immunity and monitor vaccine efficacy against SARS-CoV-2, the virus that causes COVID-19. All currently available NAb tests are lab-based and time-intensive.

SARS-CoV-2 S protein:ACE2 interaction reveals novel allosteric targets.

The spike (S) protein is the main handle for SARS-CoV-2 to enter host cells via surface angiotensin-converting enzyme 2 (ACE2) receptors. How ACE2 binding activates proteolysis of S protein is unknown. Here, using amide hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations, we have mapped the S:ACE2 interaction interface and uncovered long-range allosteric propagation of ACE2 binding to sites necessary for host-mediated proteolysis of S protein, critical for viral host entry.

Crystal structure of the periplasmic sensor domain of histidine kinase VbrK suggests indirect sensing of β-lactam antibiotics.

Bacterial two-component regulatory systems (TCS) play important roles in sensing environmental stimuli and responding to them by regulating gene expression. VbrK/VbrR, a TCS in Vibrio parahaemolyticus, confers resistance to β-lactam antibiotics through activating a β-lactamase gene. Its periplasmic sensor domain was previously suggested to detect β-lactam antibiotics by direct binding.

Structure of the human metapneumovirus polymerase phosphoprotein complex.

Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) cause severe respiratory diseases in infants and elderly adults. No vaccine or effective antiviral therapy currently exists to control RSV or HMPV infections. During viral genome replication and transcription, the tetrameric phosphoprotein P serves as a crucial adaptor between the ribonucleoprotein template and the L protein, which has RNA-dependent RNA polymerase (RdRp), GDP polyribonucleotidyltransferase and cap-specific methyltransferase activities.

Functional Evolution in Orthologous Cell-encoded RNA-dependent RNA Polymerases.

Many eukaryotic organisms encode more than one RNA-dependent RNA polymerase (RdRP) that probably emerged as a result of gene duplication. Such RdRP paralogs often participate in distinct RNA silencing pathways and show characteristic repertoires of enzymatic activities in vitro However, to what extent members of individual paralogous groups can undergo functional changes during speciation remains an open question. We show that orthologs of QDE-1, an RdRP component of the quelling pathway in Neurospora crassa, have rapidly diverged in evolution at the amino acid sequence level.

Biochemical characterization of purified OmcS, a c-type cytochrome required for insoluble Fe(III) reduction in Geobacter sulfurreducens.

Previous studies with Geobacter sulfurreducens have demonstrated that OmcS, an abundant c-type cytochrome that is only loosely bound to the outer surface, plays an important role in electron transfer to Fe(III) oxides as well as other extracellular electron acceptors. In order to further investigate the function of OmcS, it was purified from a strain that overproduces the protein. Purified OmcS had a molecular mass of 47015 Da, and six low-spin bis-histidinyl hexacoordinated heme groups.

Purification and characterization of OmcZ, an outer-surface, octaheme c-type cytochrome essential for optimal current production by Geobacter sulfurreducens.

Previous studies have demonstrated that Geobacter sulfurreducens requires the c-type cytochrome OmcZ, which is present in large (OmcZ(L); 50-kDa) and small (OmcZ(S); 30-kDa) forms, for optimal current production in microbial fuel cells. This protein was further characterized to aid in understanding its role in current production. Subcellular-localization studies suggested that OmcZ(S) was the predominant extracellular form of OmcZ.

Alignment of the c-type cytochrome OmcS along pili of Geobacter sulfurreducens.

Immunogold localization revealed that OmcS, a cytochrome that is required for Fe(III) oxide reduction by Geobacter sulfurreducens, was localized along the pili. The apparent spacing between OmcS molecules suggests that OmcS facilitates electron transfer from pili to Fe(III) oxides rather than promoting electron conduction along the length of the pili.

Evidence that OmcB and OmpB of Geobacter sulfurreducens are outer membrane surface proteins.

The c-type cytochrome (OmcB) and the multicopper protein (OmpB) required for Fe(III) oxide reduction by Geobacter sulfurreducens were predicted previously to be outer membrane proteins, but it is not clear whether they are positioned in a manner that permits the interaction with Fe(III). Treatment of whole cells with proteinase K inhibited Fe(III) reduction, but had no impact on the inner membrane-associated fumarate reduction. OmcB was digested by protease, resulting in a smaller peptide.

Two putative c-type multiheme cytochromes required for the expression of OmcB, an outer membrane protein essential for optimal Fe(III) reduction in Geobacter sulfurreducens.

Deletion of two homologous Geobacter sulfurreducens c-type cytochrome genes, omcG and omcH, decreased the rate of Fe(III) reduction and decreased the level of an outer membrane cytochrome critical for Fe(III) reduction, OmcB, without affecting its transcription. Expression of either gene restored Fe(III) reduction and OmcB expression, suggesting functional similarity.