Humoral and cellular immune responses induced by serogroup W135 meningococcal conjugate and polysaccharide vaccines.

Investigating the mechanisms by which W135 meningococcal conjugate (PSW135-TT) activates adaptive immune responses in mice can provide a comprehensive understanding of the immune mechanisms of bacterial polysaccharide conjugate vaccines. We compared B-cell and T-cell immune responses immunized with W135 meningococcal capsular polysaccharides (PSW135), tetanus toxoid (TT) and PSW135-TT in mice. The results showed that PSW135-TT could induce higher PSW135-specific and TT-specific IgG antibodies with a significant enhancement after two doses. All serum antibodies immunized with PSW135- TT had strong bactericidal activity, whereas none of the serum antibodies immunized with PSW135 had bactericidal activity. Besides, IgM and IgG antibodies immunized with PSW135-TT after two doses were positively correlated with the titer of bactericidal antibodies. We also found Th cells favored Th2 humoral immune responses in PSW135-TT, PSW135, and TT-immunized mice, especially peripheral blood lymphocytes. Furthermore, PSW135-TT and TT could effectively activate bone marrow derived dendritic cells (BMDCs) and promote BMDCs to highly express major histocompatibility complex Ⅱ (MHCⅡ), CD86 and CD40 molecules in mice, whereas PSW135 couldn't. These data verified the typical characteristics of PSW135-TT and TT as T cell dependent antigen (TD-Ag) and PSW135 as T cell independent antigen (TI-Ag), which will be very helpful for further exploration of the immune mechanism of polysaccharide-protein conjugate vaccines and improvement of the quality of bacterial polysaccharide conjugate vaccines in future.

The application of nanoparticles in point-of-care testing (POCT) immunoassays.

The Covid-19 pandemic has led to greater recognition of the importance of the fast and timely detection of pathogens. Recent advances in point-of-care testing (POCT) technology have shown promising results for rapid diagnosis. Immunoassays are among the most extensive POCT assays, in which specific labels are used to indicate and amplify the immune signal. Nanoparticles (NPs) are above the rest because of their versatile properties. Much work has been devoted to NPs to find more efficient immunoassays. Herein, we comprehensively describe NP-based immunoassays with a focus on particle species and their specific applications. This review describes immunoassays along with key concepts surrounding their preparation and bioconjugation to show their defining role in immunosensors. The specific mechanisms, microfluidic immunoassays, electrochemical immunoassays (ELCAs), immunochromatographic assays (ICAs), enzyme-linked immunosorbent assays (ELISA), and microarrays are covered herein. For each mechanism, a working explanation of the appropriate background theory and formalism is articulated before examining the biosensing and related point-of-care (POC) utility. Given their maturity, some specific applications using different nanomaterials are discussed in more detail. Finally, we outline future challenges and perspectives to give a brief guideline for the development of appropriate platforms.

Bio-mineralization of virus-like particles by metal-organic framework nanoparticles enhances the thermostability and immune responses of the vaccines.

Virus-like particle (VLPs) vaccines have been extensively studied due to their good immunogenicity and safety; however, they highly rely on cold-chain storage and transportation. Nanotechnology of bio-mineralization as a useful strategy has been employed to improve the thermal stability and immunogenicity of VLPs. A zeolitic imidazole framework (ZIF-8), a core-shell structured nanocomposite, was applied to encapsulate foot-and-mouth disease virus (FMDV) VLPs. It was found that the ZIF-8 shell enhanced the heat resistance of VLPs and promoted their ability to be taken up by cells and escape from lysosomes. The VLPs-ZIF-8 easily activated antigen-presenting cells (APCs), triggered higher secretion levels of cytokines, and elicited stronger immune responses than VLPs alone even after being treated at 37 °C for 7 days. This platform has good potential in the development of VLP-based vaccine products without transportation.

Flower-like mesoporous silica nanoparticles as an antigen delivery platform to promote systemic immune response.

Virus-like particles (VLPs), a kind of superior subunit vaccine, are assembled from the viral structural proteins with similar capsids to viruses. However, the efficiency of cell uptake is not satisfactory. We prepared flower-like mesoporous silica nanoparticles (SiNPs) with large pore channels and interior cavities to solve the problem. The highly loaded VLPs-SiNPs composites not only enhanced the stability of VLPs, but also delivered antigen to cells and improved the cellular uptake efficiency. Compared with naked VLPs, mice intramuscularly immunized with the VLPs-SiNPs composite induced higher specific antibodies, greater lymphocyte activation and higher level of cytokine secretion. Moreover, the VLPs-SiNPs composite as vaccine also promoted mucosal immune response through intranasal immune pathway. Therefore, the VLPs-SiNPs enable to induce strong cellular, humoral, and slight mucosal immune response through different immunization routes. These results are potentially useful for vaccine formulations and may provide further reference for vaccine design and delivery systems.

Biomimetic and cell-mediated mineralization of hydroxyapatite by carrageenan functionalized graphene oxide.

In bone tissue engineering, it is imperative to design multifunctional biomaterials that can induce and assemble bonelike apatite that is close to natural bone. In this study, graphene oxide (GO) was functionalized by carrageenan. The resulting GO-carrageenan (GO-Car) composite was further used as a substrate for biomimetic and cell-mediated mineralization of hydroxyapatite (HA). It was confirmed that carrageenan on the GO surface facilitated the nucleation of HA. The observation of the effect of the GO-Car on the adhesion, morphology, and proliferation of MC3T3-E1 cells was investigated. In vitro studies clearly show the effectiveness of GO-Car in promoting HA mineralization and cell differentiation. The results of this study suggested that the GO-Car hybrid will be a promising material for bone regeneration and implantation.

Selective off-on fluorescent chemosensor for detection of Fe3+ ions in aqueous media.

A Fe(3+) chemosensor L1 was successfully synthesized with a quinoline moiety bound to rhodamine 6G hydrazide. The sensor L1 shows high selectivity and sensitivity to Fe(3+) in aqueous solution in the presence of other trace metal ions in organisms, abundant cellular cations and prevalent toxic metal ions in the environment. In addition, biological imaging and micro computed tomography (MCT) technology studies have demonstrated that L1 could act as a turn-on fluorescent chemosensor for Fe(3+) in living cells.

Recognition of copper and hydrogen sulfide in vitro using a fluorescein derivative indicator.

We report the development of a fluorescein-based chemosensor (L1) for monitoring ions or micromolecules (H(2)S). Copper ions are known to be toxic at high concentrations and hydrogen sulfide induces various problems. Herein we develop a simple method for detecting Cu(II) and H(2)S with high selectivity and sensitivity. The chemosensor L1 displays on-off-on type fluorescence change with alternately added Cu(II) and H(2)S to the media along with reversible forming-separating of the complex. The potential biomedical relevance of the chemical mechanisms involved in the detection of L1 is described.

A retrievable and highly selective fluorescent probe for monitoring sulfide and imaging in living cells.

A novel selective fluorescent chemosensor based on an 8-hydroxyquinoline-appended fluorescein derivative (L1) was synthesized and characterized. Once combined with Cu(2+), it displayed high specificity for sulfide anion. Among the various anions, only sulfide anion induced the revival of fluoresecence of L1, which was quenched by Cu(2+), resulting in "off-on"-type sensing of sulfide anion. What's more, the sensor was retrievable to indicate sulfide anions with Cu(2+), and S(2-), in turn, increased. With the addition of Cu(2+), compound L1 could give rise to a visible pink-to-yellow color change and green fluorescence quenching. The resulting yellow solution could change to pink and regenerate to green fluorescence immediately upon the addition of sulfide anion; however, no changes were observed in the presence of other anions, including CN(-), P(2)O(7)(4-), and other forms of sulfate, making compound L1 an extremely selective and efficient sulfide chemosensor. The signal transduction occurs via reversible formation-separation of complex L1Cu and CuS. What's more, the biological imaging study has demonstrated that the chemosensor can detect sulfur anions in biological systems at a relatively low concentration.

Cu(2+)-selective fluorescent chemosensor based on coumarin and its application in bioimaging.

A new fluorescent sensor L1 based on coumarin was synthesized. It shows high sensitivity and selectivity toward Cu(2+) in aqueous solution. The complexation mode and corresponding quenching mechanism were elucidated by ESI-MS and DFT calculations. In addition, biological imaging studies have demonstrated that L1 can detect Cu(2+) in living cells.

A rhodamine-based "turn-on" fluorescent chemodosimeter for Cu2+ and its application in living cell imaging.

A new fluorescent probe 1, N-(Rhodamine-6G)lactam-hydrazinecarbothioamide, was synthesized as a fluorescent and colorimetric chemodosimeter in aqueous solution for Cu(2+). Following Cu(2+)-promoted ring opening, redox and hydrolysis reactions, comparable amplifications of absorption and fluorescence signals were observed upon addition of Cu(2+); this suggests that chemodosimeter 1 effectively avoided the fluorescence quenching caused by the paramagnetic nature of Cu(2+). Importantly, 1 can selectively recognize Cu(2+) in aqueous media in the presence of other trace metal ions in organisms, abundant cellular cations and the prevalent toxic metal ions in the environment with high sensitivity (detection limit <3 ppb) and a rapid response time (<2 min). In addition, the biological imaging study has demonstrated that 1 can detect Cu(2+) in the living cells.