Influenza B virus causes considerable disease burden worldwide annually, highlighting the limitations of current influenza vaccines and antiviral drugs. In recent years, broadly neutralizing antibodies (bnAbs) against hemagglutinin (HA) have emerged as a new approach for combating influenza. We describe the generation and characterization of a chimeric monoclonal antibody, C12G6, that cross-neutralizes representative viruses spanning the 76 years of influenza B antigenic evolution since 1940, including viruses belonging to the Yamagata, Victoria, and earlier lineages. Notably, C12G6 exhibits broad cross-lineage hemagglutination inhibition activity against influenza B viruses and has higher potency and breadth of neutralization when compared to four previously reported influenza B bnAbs. In vivo, C12G6 confers stronger cross-protection against Yamagata and Victoria lineages of influenza B viruses in mice and ferrets than other bnAbs or the anti-influenza drug oseltamivir and has an additive antiviral effect when administered in combination with oseltamivir. Epitope mapping indicated that C12G6 targets a conserved epitope that overlaps with the receptor binding site in the HA region of influenza B virus, indicating why it neutralizes virus so potently. Mechanistic analyses revealed that C12G6 inhibits influenza B viruses via multiple mechanisms, including preventing viral entry, egress, and HA-mediated membrane fusion and triggering antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity responses. C12G6 is therefore a promising candidate for the development of prophylactics or therapeutics against influenza B infection and may inform the design of a truly universal influenza vaccine.

No abstract

Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus that establishes lifelong persistence and is related to multiple diseases, including cancers. Neutralizing antibodies (NAbs) have proven to be highly effective in preventing EBV infection and subsequent diseases.

Epstein-Barr virus (EBV) infects more than 90% of the world’s adult population and accounts for a significant cancer burden of epithelial and B cell origins. Glycoprotein B (gB) is the primary fusogen essential for EBV entry into host cells. Here, we isolated two EBV gB-specific neutralizing antibodies, 3A3 and 3A5; both effectively neutralized the dual-tropic EBV infection of B and epithelial cells. In humanized mice, both antibodies showed effective protection from EBV-induced lymphoproliferative disorders. Cryoelectron microscopy analyses identified that 3A3 and 3A5 bind to nonoverlapping sites on domains D-II and D-IV, respectively. Structure-based mutagenesis revealed that 3A3 and 3A5 inhibit membrane fusion through different mechanisms involving the interference with gB-cell interaction and gB activation. Importantly, the 3A3 and 3A5 epitopes are major targets of protective gB-specific neutralizing antibodies elicited by natural EBV infection in humans, providing potential targets for antiviral therapies and vaccines.

Epstein–Barr virus (EBV) is the first reported oncogenic virus and infects more than 90% of adults worldwide. EBV can establish a latent infection in B lymphocytes which is essential for persistence and transmission. Glycoprotein gp42 is an indispensable member of the triggering complex for EBV entry into a B cell. The N-terminal region of gp42 plays a key role in binding to gH/gL and triggering subsequent membrane fusion. However, no antibody has been reported to recognize this region and the immunogenicity of gp42 N-domain remains unknown. In the present study, we have generated a panel of nine mAbs against the gp42 N-terminal region (six mAbs to gp42-44-61aa and three mAbs to gp42-67-81aa). These mAbs show excellent binding activity and recognize different key residues locating on the gp42 N-domain. Among the nine mAbs, 4H7, 4H8 and 11G10 cross-react with rhLCV-gp42 while other mAbs specifically recognize EBV-gp42. Our newly obtained mAbs provide a useful tool for investigating the gp42 function and viral infection mechanism of γ-Herpesvirus. Furthermore, we assess the immunogenicity of the gp42 N-terminal region using the HBc149 particle as a carrier protein. The chimeric VLPs can induce high antibody titers and elicit neutralizing humoral responses to block EBV infection. More rational and effective designs are required to promote the gp42-N terminal region to become an epitope-based vaccine.

The Janus membrane has a huge prospect for personal comfortable protection. However, there still is a huge imbalance between the comfort and protection of the existing Janus membrane. There is an urgent need to further improve the comprehensive performance of the protective membrane to realize both protection and comfort. Herein, we report the Janus membrane with directional water transport capacity and dust rejection performance by compounding the polyvinyl chloride hydrophobic nanofiber membrane and polyamide-6 blended polyvinyl pyrrolidone hydrophilic nanofiber membrane. This Janus composite nanofiber membrane exhibited an excellent dust rejection efficiency of 99.99%, air permeability of 42.15 mm/s, which was 76 times that of the commercial waterproof and breathable PTFE membrane, water vapor transmission rate of 4.89 kg/(m2 × 24 h), and accumulative one-way transport capacity of 888.7%. In addition, the breakthrough pressure of the Janus membrane in the reverse direction (i.e., hydrophilic layer to hydrophobic layer) was four times that in the positive direction (i.e., hydrophobic layer to hydrophilic layer), suggesting it to be a potential substrate for comfortable bioprotection with a comprehensive protection capability.

Self-pumping wound dressings with directional water transport ability have been widely studied for their function of directional extraction of excessive biofluid from wounds while keeping the wound in a moderately humid environment to realize rapid wound healing. However, the existing solutions have not paid close attention to the fabrication of a nonirritating hydrophobic layer facing the wounds, which may cause irritation to wounds and thereby further worsen inflammation. Herein, a flexible and elastic thermoplastic polyurethane (TPU) hydrophobic microfiber mesh (TPU-HMM) produced by melt electrospinning (MES) is reported. The TPU-HMM was compounded to a hydrophilic nanofiber membrane, which was fabricated by blending with polyamide 6 and poly­(ethylene glycol) (PA6-PEG) to form a composite self-pumping dressing, for which the breakthrough pressure in a reverse direction was 12.8 times than that in a positive direction and the forward water transmission rate was increased by 700%. It shows good directional water transport ability and is expected to absorb excessive biofluid of the wounds. This solvent-free and easy-process TPU-HMM provides a new strategy for the development of functional self-pumping textiles, and the solvent-free fabrication method for fibers, which eliminates the potential toxicity brought by solvent residues, offers more possibilities for its applications in biomedicine.

High-performance air filtration was the key to health protection from biological and ultrafine dust pollution. A self-supporting, three-dimensional (3D) nanofibrous membrane with curled pattern was electrospun for the filtration, of which the micro-fluffy structure displayed high-filtration efficiency and low-pressure drop. The flow field in the 3D filtration membrane was simulated to optimize the process parameters to increase the filtration performance. The qualification factor increased from 0.0274 Pa−1 to 0.0309 Pa−1 by 12.77% after the optimization of the electrospinning parameters. The best filtration efficiency and pressure drop were 93.6% and 89.0 Pa, separately. This work provides a new strategy to fabricate 3D structures through the construction of fiber morphology and promotes further improvement of air filtration performance of fibrous filters.