Metal-insulator-semiconductor photoelectrodes for enhanced photoelectrochemical water splitting.

Photoelectrochemical (PEC) water splitting provides a scalable and integrated platform to harness renewable solar energy for green hydrogen production. The practical implementation of PEC systems hinges on addressing three critical challenges: enhancing energy conversion efficiency, ensuring long-term stability, and achieving economic viability. Metal-insulator-semiconductor (MIS) heterojunction photoelectrodes have gained significant attention over the last decade for their ability to efficiently segregate photogenerated carriers and mitigate corrosion-induced semiconductor degradation. This review discusses the structural composition and interfacial intricacies of MIS photoelectrodes tailored for PEC water splitting. The application of MIS heterostructures across various semiconductor light-absorbing layers, including traditional photovoltaic-grade semiconductors, metal oxides, and emerging materials, is presented first. Subsequently, this review elucidates the reaction mechanisms and respective merits of vacuum and non-vacuum deposition techniques in the fabrication of the insulator layers. In the context of the metal layers, this review extends beyond the conventional scope, not only by introducing metal-based cocatalysts, but also by exploring the latest advancements in molecular and single-atom catalysts integrated within MIS photoelectrodes. Furthermore, a systematic summary of carrier transfer mechanisms and interface design principles of MIS photoelectrodes is presented, which are pivotal for optimizing energy band alignment and enhancing solar-to-chemical conversion efficiency within the PEC system. Finally, this review explores innovative derivative configurations of MIS photoelectrodes, including back-illuminated MIS photoelectrodes, inverted MIS photoelectrodes, tandem MIS photoelectrodes, and monolithically integrated wireless MIS photoelectrodes. These novel architectures address the limitations of traditional MIS structures by effectively coupling different functional modules, minimizing optical and ohmic losses, and mitigating recombination losses.

Crystalline Olefin-Linked Chiral Covalent Organic Frameworks as a Platform for Asymmetric Catalysis.

The construction of olefin-linked chiral covalent organic frameworks (COFs) with high crystallinity is highly desirable while remains great challenge due to the poor reversibility of the formation reaction for the olefin linkages during the in situ structural self-healing process. Herein, we successfully synthesized two sets of enantiomeric olefin-linked COFs. The chiral catalytic groups are uniformly distributed on the pore walls of COFs, resulting in the full exposure of catalytic sites to the reactants in asymmetric catalysis. The as-prepared (R)/(S)-CCOF8 exhibits excellent catalytic performance with exceeding 99 % enantiomeric excess in the enantioselective electrophilic amination reaction. Moreover, the heterogeneous chiral catalysts are conveniently recycled and could maintain the performance after ten catalytic cycles. Our findings expand the scope to construct stable and crystalline chiral COFs for the asymmetric catalysis.

3D Crown Ether Covalent Organic Framework as Interphase Layer toward High-Performance Lithium Metal Batteries.

The practical application of lithium (Li) metal batteries is inhibited by accumulative Li dendrites and continuous active Li consumption during cycling, which results in a low Coulombic efficiency and short lifetime. Constructing artificial solid-electrolyte interphase (SEI) layer in Li anode, such as 2D covalent organic frameworks (COFs), is an effective strategy to restrain the formation of Li dendrites and improve cycling performance. However, the exploration of 3D COFs as protecting layers is rarely reported, because of the preconception that the interconnect pores in 3D COFs eventually cause Li dendrites in disordered direction. 3D crown ether-based COF with ffc topology as interphase layer, in which the crown ether units are arranged in parallel and vertical orientation along the electrode, is demonstrated. The strong coupling effect between the crown ether and Li+ accelerates Li+ diffusion kinetics and enables homogeneous Li+ flux, resulting in a high Li+ transference number of 0.85 and smooth Li deposition in 3D direction. Li/COF-Cu cells display a lower Li-nucleation overpotential (17.4 mV) and high average Coulombic efficiency of ≈98.6% during 340 cycles with COF incorporation. This work gives a new insight into designing COFs for energy storage systems.

Modulating Skeletons of Covalent Organic Framework for High-Efficiency Gold Recovery.

Covalent organic frameworks (COFs) have attracted considerable attention as adsorbents for capturing and separating gold from electronic wastes. To enhance the binding capture efficiency, constructing hydrogen-bond nanotraps along the pore walls was one of the most widely adopted approaches. However, the development of absorbing skeletons was ignored due to the weak binding ability of the gold salts (Au). Herein, we demonstrated skeleton engineering to construct highly efficiently absorbs for Au capture. The strong electronic donating feature of diarylamine units enhanced the electronic density of binding sites (imine-linkage) and thus resulted in high capacities over 1750 mg g-1 for all three COFs. Moreover, the absorbing performance was further improved via the ionization of diarylamine units. The ionic COF achieved 90 % of the maximal adsorption capacity, 1.63 times of that from the charge-neutral COF within ten minutes, and showed remarkable uptakes of 1834 mg g-1 , exceptional selectivity (97.45 %) and cycling stability. The theoretical calculation revealed the binding sites altering from imine bonds to ionic amine sites after ionization of the frameworks, which enabled to bind the AuCl4 - via coulomb force and contributed to enhanced absorbing kinetics. This work inspires us to design molecular/ionic capture based on COFs.

Hexatopic Vertex-Directed Approach to Vinylene-Linked Covalent Organic Frameworks with Heteroporous Topologies.

A D3h-symmetric hexatopic monomer was first prepared by attaching the three-fold ditopic moiety 2,6-dimethylpyridine to the meta-positions of a phenyl ring. It was further condensed at its six pyridylmethyl carbons with linear ditopic aromatic dialdehydes, resulting in two vinylene-linked COFs with heteroporous topologies, as revealed by powder X-ray diffraction (PXRD), nitrogen sorption, and pore-size distribution analyses, as well as transmission electron microscopy (TEM) image. The linear- and cross-conjugations, respectively, arising from the 2,6-linked pyridines and meta-linked phenylenes in the hexatopic nodes rendered the resultant COFs with well-patterned π-delocalization, allowing for efficiently catalyzing the bromination of aromatic derivatives with the pore-size-dependent conversion yields and regioselectivity under the irradiation of green light.

3D network with channel excitation and knowledge distillation for action recognition.

Modern action recognition techniques frequently employ two networks: the spatial stream, which accepts input from RGB frames, and the temporal stream, which accepts input from optical flow. Recent researches use 3D convolutional neural networks that employ spatiotemporal filters on both streams. Although mixing flow with RGB enhances performance, correct optical flow computation is expensive and adds delay to action recognition. In this study, we present a method for training a 3D CNN using RGB frames that replicates the motion stream and, as a result, does not require flow calculation during testing. To begin, in contrast to the SE block, we suggest a channel excitation module (CE module). Experiments have shown that the CE module can improve the feature extraction capabilities of a 3D network and that the effect is superior to the SE block. Second, for action recognition training, we adopt a linear mix of loss based on knowledge distillation and standard cross-entropy loss to effectively leverage appearance and motion information. The Intensified Motion RGB Stream is the stream trained with this combined loss (IMRS). IMRS surpasses RGB or Flow as a single stream; for example, HMDB51 achieves 73.5% accuracy, while RGB and Flow streams score 65.6% and 69.1% accuracy, respectively. Extensive experiments confirm the effectiveness of our proposed method. The comparison with other models proves that our model has good competitiveness in behavior recognition.

2,4,6-Trimethylpyridine-Derived Vinylene-Linked Covalent Organic Frameworks for Confined Catalytic Esterification.

Knoevenagel condensation is a powerful tool for the construction of vinylene-linked covalent organic frameworks. Herein, we established a concise approach to vinylene-linked COFs by Knoevenagel condensation at the multi-methyl groups of a pyridine ring through in situ formation of an N-acyl pyridinium cation in the presence of various acylating reagents. Following this strategy, two vinylene-linked COFs were constructed using 2,4,6-trimethylpyridine and multi-aldehyde-substituted aromatic derivatives as monomers. The resultant COFs are highly crystalline and assembled into hexagonal lattices with specific surface areas as large as 1915 m2 g-1 (vs. 1972 m2 g-1 of the theoretical value). The stable and abundant pyridine-decorated regular nanochannels within the COFs allow for catalyzing the esterification of several pharmaceutical intermediates with distinct spatially confined selectivity and recyclability, representing an environmentally friendly catalytic organic transformation.

Differential Effects of Toll-Like Receptor Signaling on the Activation of Immune Responses in the Upper Respiratory Tract.

Vaccination through the upper respiratory tract (URT) is highly effective for the prevention of respiratory infectious diseases. Toll-like receptor (TLR)-based adjuvants are immunostimulatory and considered potential adjuvant candidates. However, the patterns of immune response to different TLRs at the URT have not been revealed. In this study, SPF mice were preexposed to TLR agonists intranasally to simulate the status of humans. Inflammatory response to TLR agonists and TLR signal-mediated adaptive immune responses were analyzed. The results revealed that similar to human tonsils, inflammatory response to stimulation with TLR4 or TLR2 agonist was attenuated in agonist-exposed mice but not in mice without this exposure. In contrast, TLR9 or TLR3 agonist preexposure did not affect the inflammatory response to restimulation by matching agonists. For the adaptive immune response, after agonist preexposure the antibody response to antigens adjuvanted with TLR4 or TLR2 agonist was substantially restricted, whereas, both antibody and T cell responses to antigens adjuvanted with TLR9 or TLR3 agonist were activated as robustly as in mice without agonist exposure. Moreover, we demonstrate that the mechanisms underlying the differential activation of TLRs are regulated at the level of TLR expression in innate and adaptive immune cells. These results indicate that TLRs on the cell surface (TLR4 and 2) and in the endolysosomal compartments (TLR9 and 3) display distinct immune response patterns. The findings provide important information for the use of TLR agonists as mucosal adjuvants and enhance our understanding of immune responses to bacterial and viral infections in the respiratory mucosa. IMPORTANCE Agonists of TLRs are potential adjuvant candidates for mucosal vaccination. We demonstrated that the TLR-mediated inflammatory and antibody responses in the URT of SPF mice exposed to extracellular TLR agonists were substantially restricted. In contrast, inflammatory and adaptive immune responses, including B and T cell activation, were not desensitized in mice exposed to intracellular TLR agonists. The distinct responsive patterns of extra and intracellular TLRs regulated at TLR expression in immune cells. The results indicated that TLRs differentially impact the innate and adaptive immune response in the URT, which contributes to the selection of TLR-based mucosal adjuvants and helps understand the difference between the immune response in bacterial and viral infections.

Synthesis of Vinylene-Linked Covalent Organic Frameworks by Monomer Self-Catalyzed Activation of Knoevenagel Condensation.

Reticular chemistry based on thermodynamically controlled linking modes and numerous organic building blocks has constituted versatile crystalline frameworks in molecular-level precision. However, vinylene-linked covalent organic frameworks (COFs) are still quite far from flexible tailoring in either their structures or topologies, due to the lack of monomers with sufficient activities. Herein, we establish a strategy to synthesize vinylene-linked COFs via Knoevenagel condensation between a tetratopic monomer 2,2',6,6'-tetramethyl-4,4'-bipyridine (TMBP) and linear aromatic dialdehydes in a mixed solvent of benzoic anhydride and benzoic acid. Mechanistic investigation suggests that the condensation was promoted by a pyridine self-catalyzed benzoylation upon the cleavage of benzoic anhydride solvent molecules. The layered structures of the resultant COFs are highly crystallized into orthorhombic lattices with vertically aligned AA stacking modes, delivering high surface areas up to 1560 m2 g-1. The π-extended conjugated skeletons comprising para-bipyridyl units and vinylene linkages endow these COFs with substantial semiconducting properties, releasing visible-light-stimulated catalytic activity in water-splitting hydrogen evolution with a rate as high as 3230 µmol g-1 h-1.

Immunity to Sda1 Protects against Infection by Sda1+ and Sda1- Serotypes of Group A Streptococcus.

Group A Streptococcus (GAS) causes a variety of diseases globally. The DNases in GAS promote GAS evasion of neutrophil killing by degrading neutrophil extracellular traps (NETs). Sda1 is a prophage-encoded DNase associated with virulent GAS strains. However, protective immunity against Sda1 has not been determined. In this study, we explored the potential of Sda1 as a vaccine candidate. Sda1 was used as a vaccine to immunize mice intranasally. The effect of anti-Sda1 IgG in neutralizing degradation of NETs was determined and the protective role of Sda1 was investigated with intranasal and systemic challenge models. Antigen-specific antibodies were induced in the sera and pharyngeal mucosal site after Sda1 immunization. The anti-Sda1 IgG efficiently prevented degradation of NETs by supernatant samples from different GAS serotypes with or without Sda1. Sda1 immunization promoted clearance of GAS from the nasopharynx independent of GAS serotypes but did not reduce lethality after systemic GAS challenge. Anti-Sda1 antibody can neutralize degradation of NETs by Sda1 and other phage-encoded DNases and decrease GAS colonization at the nasopharynx across serotypes. These results indicate that Sda1 can be a potential vaccine candidate for reduction in GAS reservoir and GAS tonsillitis-associated diseases.

Heteroatom-Embedded Approach to Vinylene-Linked Covalent Organic Frameworks with Isoelectronic Structures for Photoredox Catalysis.

Embedding heteroatoms into the main backbones of polymeric materials has become an efficient tool for tailoring their structures and improving their properties. However, owing to comparatively harsh heteroatom-doping conditions, this has rarely been explored in covalent organic frameworks (COFs). Herein, upon aldol condensation of a trimethyl-substituted pyrylium salt with a tritopic aromatic aldehyde, a two-dimensional oxonium-embedded COF with vinylene linkages was achieved, which was further converted to a neutral pyridine-cored COF by in situ replacement of oxonium ions with nitrogen atoms under ammonia treatment. The two heteroatom-embedded COFs are conceptually isoelectronic with each other, featuring similar geometric structures but different electronic structures, rendering them capable of catalyzing the visible-light-promoted multi-component synthesis of tri-substituted pyridine derivatives with good recyclability.

Synthesis of Ionic Vinylene-Linked Covalent Organic Frameworks through Quaternization-Activated Knoevenagel Condensation.

We developed a simple approach to synthesizing ionic vinylene-linked two-dimensional covalent organic frameworks (COFs) through a quaternization-promoted Knoevenagel condensation at three aromatic methyl carbon atoms of N-ethyl-2,4,6-trimethylpyridinium halide with multitopic aromatic aldehyde derivatives. The resultant COFs exhibited a honeycomb-like structure with high crystallinity and surface areas as large as 1343 m2 g-1 . The regular shape-persistent nanochannels and the positively charged polymeric frameworks allowed the COFs to be uniformly composited with linear polyethylene oxide and lithium salt, displaying ionic conductivity as high as 2.72×10-3  S cm-1 .

Ordered Bicontinuous Mesoporous Polymeric Semiconductor Photocatalyst.

Owning triply periodic minimal surfaces and three-dimensional (3D) interconnected pores, bicontinuous porous materials have drawn enormous attention due to their great academic interest and potential applications in many fields including energy and catalysis. However, their synthesis has remained a great challenge. Here, we demonstrate the synthesis of a bicontinuous porous organic semiconductor photocatalyst, which involves the preparation of SiO2 with a shifted double diamond (DD) structure through solvent evaporation-induced self-assembly of a polystyrene-block-poly(ethylene oxide) diblock copolymer and tetraethyl orthosilicate, followed by SiO2-templated self-condensation of melamine monomers in a vacuum. Strikingly, the resultant DD-structured graphitic carbon nitride (g-CN) possesses two sets of 3D continuous mesopores with a mean diameter of 14 nm, which afford a high specific surface area of 131 m2 g-1 and an optical band gap of 2.8 eV. Being a visible-light-driven photocatalyst, the bicontinuous mesoporous g-CN exhibits high catalytic activity for water splitting to generate H2 (6831 µmol g-1 h-1) with excellent cycling stability. This study provides a protocol for the construction of ordered mesoporous materials containing 3D continuous channels, which holds promise for catalysis applications.

Vinylene-Linked Covalent Organic Frameworks (COFs) with Symmetry-Tuned Polarity and Photocatalytic Activity.

The polarity of a semiconducting molecule affects its intrinsic photophysical properties, which can be tuned by varying the molecular geometry. Herein, we developed a D3h -symmetric tricyanomesitylene as a new monomer which could be reticulated into a vinylene-linked covalent organic framework (g-C54 N6 -COF) via Knoevenagel condensation with another D3h -symmetric monomer 2,4,6-tris(4'-formyl-biphenyl-4-yl)-1,3,5-triazine. Replacing tricyanomesitylene with a C2v -symmetric 3,5-dicyano-2,4,6-trimethylpyridine gave a less-symmetric vinylene-linked COF (g-C52 N6 -COF). The octupolar conjugated characters of g-C54 N6 -COF were reflected in its scarce solvatochromic effects either in ground or excited states, and endowed it with more promising semiconducting behavior as compared with g-C52 N6 -COF, such as enhanced light-harvesting and excellent photo-induced charge generation and separation. Along with the matched energy level, g-C54 N6 -COF enabled the two-half reactions of photocatalytic water splitting with an average O2 evolution rate of 51.0 µmol h-1 g-1 and H2 evolution rate of 2518.9 µmol h-1 g-1 . Such values are among the highest of state-of-the-art COF photocatalysts.

Vinylene-Bridged Two-Dimensional Covalent Organic Frameworks via Knoevenagel Condensation of Tricyanomesitylene.

Vinylene-bridged covalent organic frameworks (COFs) have shown great potential for advanced applications because of their high chemical stability and intriguing semiconducting properties. Exploring new functional monomers available for the reticulation of vinylene-bridged COFs and establishing effective reaction conditions are extremely desired for enlarging the realm of this kind of material. In this work, a series of vinylene-bridged two-dimensional (2D) COFs are synthesized by Knoevenagel condensation of tricyanomesitylene with ditopic or tritopic aromatic aldehydes. With use of appropriate secondary amines as catalysts, high-crystalline vinylene-bridged COFs were achieved, exhibiting long-range ordered structures, well-defined nanochannels, high surface areas (up to 1231 m2 g-1), and excellent photophysical properties. Under a low loading amount and short reaction time, they enable aerobic photocatalytic transformation of arylboronic acids to phenols with high efficiency and excellent recyclability. This work demonstrates a new functional monomer, tricyanomesitylene, feasible for the general synthesis of vinylene-bridged COFs with potential application in photocatalytic organic transformation, which instigates further research on such kind of material.

Trimethyltriazine-derived olefin-linked covalent organic framework with ultralong nanofibers.

Two-dimensional (2D) olefin-linked covalent organic frameworks (COFs) with excellent π-electron communication and high stability are emerging as promising crystalline polymeric materials. However, because of the limited species of COFs, their characteristics, processability and potential applications have not been completely understood and explored. In this work, we prepared two novel olefin-linked 2D COFs through Knoevenagel condensation of 2,4,6-trimethyl-1,3,5-triazine with tritopic triazine-cored aldehydes. The resulting COFs exhibit highly crystalline honeycomb-like structures stacked from hexagonal-latticed polymeric layers and display well-defined nanofibrillar morphologies with the uniform diameters of ca. 80 nm and ultra-lengths up to several micrometers. Such COF nanofibers can be readily composited with carbon nanotubes into high-quality continuous thin films, which are further compacted by a typical hot-pressing process to enhance their densities and mechanical strength without changing their fibrous microstructures. Such film-fabricated interdigital microelectrodes and the ionogel electrolyte are assembled into planar micro-supercapacitors (MSCs), which exhibit an outstanding areal capacitance of 44.3 mF cm-2, large operating voltage window of 2.5 V, high volumetric energy density of 38.5 mWh cm-3 as well as excellent cycling stability.

Long-lasting protective immunity against H7N9 infection is induced by intramuscular or CpG-adjuvanted intranasal immunization with the split H7N9 vaccine.

There is an urgent need for efficient vaccines against the highly pathogenic avian influenza A viral strain H7N9. The duration and intensity of the immune response to H7N9 critically impacts the epidemiology of influenza viral infection at the population level. However, the insufficient immunogenicity of H7N9 raises concerns about vaccine efficacy. In this study, we evaluated the impact of immunization routes and the adjuvant CpG on the immune response to a split H7N9 vaccine in mice. Determination of humoral and cellular responses to the vaccine revealed that after four vaccine doses, high titers of H7N9-specific serum IgG, determined by the influenza hemagglutination inhibition (HI) assay, were induced through the intramuscular (i.m.) route and lasted for at least 40 weeks. CpG-adjuvanted immunization increased the levels of long-lived IFN-γ+ T cells and raised the Th1-biased IgG2a/IgG1 response ratio. In addition, aside from mucosal IgA, CpG-adjuvanted intranasal (i.n.) immunization elicited serum IgG and cellular responses of a similar duration and intensity to CpG-adjuvanted i.m. immunization. Mouse challenge assays demonstrated that 24 weeks following i.m. immunization without CpG or CpG-adjuvanted immunization through the i.m. or i.n. routes, both offered a high level of protection against H7N9 infection. These results indicate that efficient long-term protection against H7N9 can be achieved via the optimization of vaccination strategies, such as immunization doses, routes, and adjuvants.

A Multicomponent Vaccine Provides Immunity against Local and Systemic Infections by Group A Streptococcus across Serotypes.

Group A streptococcus (GAS) species are responsible for a broad spectrum of human diseases, ranging from superficial to invasive infections, and are associated with autoimmune disorders. There is no commercial vaccine against GAS. The clinical manifestations of GAS infection may be attributable to the large repertoire of virulence factors used selectively in different types of GAS disease. Here, we selected five molecules, highly conserved among GAS serotypes, and involved in different pathogenic mechanisms, as a multicomponent vaccine, 5CP. Intranasal (i.n.) immunization with 5CP protected mice against both mucosal and systemic GAS infection across serotypes; the protection lasted at least 6 months. Immunization of mice with 5CP constrained skin lesion development and accelerated lesion recovery. Flow cytometry and enzyme-linked immunosorbent assay analyses revealed that 5CP induced Th17 and antibody responses locally and systemically; however, the Th17 response induced by 5CP resolved more quickly than that to GAS when challenge bacteria were cleared, suggesting that 5CP is less likely to cause autoimmune responses. These findings support that immunization through the i.n. route targeting multiple nonredundant virulence factors can induce immunity against different types of GAS disease and represents an alternative strategy for GAS vaccine development, with favorable efficacy, coverage, duration, and safety.IMPORTANCE GAS is among the most common human pathogens and causes a wide variety of diseases, likely more than any other microorganism. The diverse clinical manifestations of GAS may be attributable to its large repertoire of virulence factors that are selectively and synergistically involved in streptococcal pathogenesis. To date, GAS vaccines have not been successful due to multiple serotypes and postinfection sequelae associated with autoimmunity. In this study, five conserved virulence factors that are involved in GAS pathogenesis were used as a combined vaccine. Intranasal immunization with this vaccine induced humoral and cellular immune responses across GAS serotypes and protected against mucosal, systemic, and skin infections. The significance of this work is to demonstrate that the efficacy of GAS vaccines can be achieved by including multiple nonredundant critical virulence factors and inducing local and systemic immunity. The strategy also provides valuable insights for vaccine development against other pathogens.

Semiconducting 2D Triazine-Cored Covalent Organic Frameworks with Unsubstituted Olefin Linkages.

Establishing an sp2-carbon-bonding pattern is one of the efficient accesses to various organic semiconducting materials. However, the less-reversible carbon-carbon bond formation makes it still challenging to spatially construct a well-defined organic framework with π-extended two-dimensional (2D) structure through solution process. Here, a Knoevenagel condensation approach to synthesize two new 2D covalent organic frameworks (COFs) connected by unsubstituted carbon-carbon double bond linkages through activating the methyl carbons of a 2,4,6-trimethyl-1,3,5-triazine monomer is presented. The resulting sp2-carbon-linked triazine-cored 2D sheets are vertically stacked into high-crystalline honeycomb-like structures, endowing this kind of COF with extended π-delocalization, tunable energy levels, as well as high surface areas, regular open channels, and chemical stabilities. On the other hand, their microfibrillar morphologies allow for the facile manipulation of thin films as photoelectrodes without additive. Accordingly, such kinds of COF-based photoelectrodes exhibit photocurrents up to ∼45 µA cm-2 at 0.2 V vs RHE as well as rapid charge transfer rates, in comparison with imine-linked COF-based photoelectrodes. In addition, both COFs are applicable for conducting photocatalytic hydrogen generation from water splitting by visible-light irradiation.

Intranasal Vaccination With Multiple Virulence Factors Promotes Mucosal Clearance of Streptococcus suis Across Serotypes and Protects Against Meningitis in Mice.

BACKGROUND: Streptococcus suis is an emerging zoonotic agent. Its natural habitat is the tonsils, which are the main portals of S. suis entry into the bloodstream of pigs. The remarkable variability of the bacteria and complex pathogenic mechanisms make the development of a vaccine a difficult task. METHOD: Five conserved virulence factors involved in critical events of S. suis pathogenesis were combined and used as an intranasal vaccine (V5). The effect of V5 was investigated with intranasal and systemic challenge models. RESULTS: V5 induced antibody and T-cell responses at the mucosal site and systemically. The immunity promoted clearance of S. suis from the nasopharynx independent of S. suis serotypes and reduced lethality after systemic challenge with S. suis serotype 2. Moreover, mice that survived sepsis from intravenous infection developed meningitis, whereas none of these mice showed neuropathological symptoms after V5 receipt. CONCLUSION: Intranasal immunization with multiple conserved virulence factors decreases S. suis colonization at the nasopharynx across serotypes and inhibits the dissemination of the bacteria in the host. The protective mucosal immunity effects would potentially reduce the S. suis reservoir and prevent S. suis disease in pigs.