ABSTRACT
Self-adjuvanting protein vaccines have been proved to be highly immunogenic with efficient codelivery of adjuvant and antigen. Current protein vaccines with built-in adjuvants are all modified at the peptide backbone of antigen protein, which could not achieve minor epitope interference and adjuvant multivalency at the same time. Herein, we developed a new conjugate strategy to construct effective adjuvant-protein vaccine with adjuvant cluster effect and minimal epitope interference. The toll-like receptor 7 agonist (TLR7a) is covalently conjugated on the terminal sialoglycans of SARS-CoV-2-S1 protein, leading to intracellular release of the small-molecule stimulators with greatly reduced risks of systemic toxicity. The resulting TLR7a-S1 conjugate elicited strong activation of immune cells in vitro, and potent antibody and cellular responses with a significantly enhanced Th1-bias in vivo. TLR7a-S1-induced antibody also effectively cross-neutralized all variants of concern. This sialoglycoconjugation approach to construct protein conjugate vaccines will have more applications to combat SARS-CoV-2 and other diseases.
Subject(s)
COVID-19 Vaccines , COVID-19 , Humans , COVID-19/prevention & control , SARS-CoV-2 , Adjuvants, Immunologic , Antigens , Adjuvants, Pharmaceutic , EpitopesABSTRACT
Safe and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants are the best approach to successfully combat the COVID-19 pandemic. The receptor-binding domain (RBD) of the viral spike protein is a major target to develop candidate vaccines. α-Galactosylceramide (αGalCer), a potent invariant natural killer T cell (iNKT) agonist, was site-specifically conjugated to the N-terminus of the RBD to form an adjuvant-protein conjugate, which was anchored on the liposome surface. This is the first time that an iNKT cell agonist was conjugated to the protein antigen. Compared to the unconjugated RBD/αGalCer mixture, the αGalCer-RBD conjugate induced significantly stronger humoral and cellular responses. The conjugate vaccine also showed effective cross-neutralization to all variants of concern (B.1.1.7/alpha, B.1.351/beta, P.1/gamma, B.1.617.2/delta, and B.1.1.529/omicron). These results suggest that the self-adjuvanting αGalCer-RBD has great potential to be an effective COVID-19 vaccine candidate, and this strategy might be useful for designing various subunit vaccines.
Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/therapy , Galactosylceramides/therapeutic use , Peptide Fragments/therapeutic use , SARS-CoV-2/immunology , Vaccines, Conjugate/therapeutic use , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/therapeutic use , Animals , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , COVID-19 Vaccines/chemistry , COVID-19 Vaccines/immunology , Female , Galactosylceramides/chemistry , Galactosylceramides/immunology , Immunity, Humoral/drug effects , Immunity, Innate/drug effects , Interferon-gamma/metabolism , Liposomes/chemistry , Liposomes/immunology , Liposomes/therapeutic use , Mice, Inbred BALB C , Peptide Fragments/chemistry , Peptide Fragments/immunology , Protein Domains , Spike Glycoprotein, Coronavirus/chemistry , Spike Glycoprotein, Coronavirus/immunology , Spike Glycoprotein, Coronavirus/therapeutic use , Vaccines, Conjugate/chemistry , Vaccines, Conjugate/immunologyABSTRACT
In this study, a new ecological dam based on the microbial fuel cell principle (MFCED) was designed to remove pollutants from river sediments and water bodies. Sediment organics were better removed in the MFCED mode in comparison with the other two modes (ecological dam with open circuit (OCED) and ecological dam filled with gravel in cathode chamber (GMFCED)). The difference of nitrogen source in water had little effect on the removal of chemical oxygen demand (COD) (70-80%), while nitrate was more readily removed in the MFCED. The voltage curve and power curve were measured to understand the bioelectricity generation of MFCED. During the stable operation phase of MFCED, the voltage was stabilized between 0.09-0.15 V. The results of high-throughput sequencing indicated that the anode and cathode diversities of MFCED were more than the other systems, and the species diversity of the anode was more than that of the cathode in the MFCED. Graphical abstract.
Subject(s)
Bioelectric Energy Sources , Environmental Restoration and Remediation/methods , Waste Disposal, Fluid/methods , Water Purification/methods , Bioelectric Energy Sources/microbiology , Biological Oxygen Demand Analysis , Electricity , Electrodes/microbiology , Microbiota , Nitrogen/isolation & purification , Water Pollutants, Chemical/isolation & purificationABSTRACT
This study mainly focuses on the preparation, characterization, and sorption performance for Cu(II) and Zn(II) by using nano-alumina material (NA) synthesized through the sol-gel method. The SEM, EDS, FT-IR, and XRD analysis methods were implemented to identify the micromorphology and crystal structure of the synthesized NA absorbent and its structure after the adsorbing procedure. The effect of effective variables including various absorbent dose, contact time, initial ion concentration, and temperature on the removal of Cu(II) and Zn(II) from aqueous solution by using NA was investigated through a single factor experiment. Kinetic studies indicated that adsorption of copper and zinc ions by NA was chemical adsorption. The adsorption isotherm data were fitted by Langmuir (R2: 0.919, 0.914), Freundlich (R2: 0.983, 0.993), and Temkin (R2: 0.876, 0.863) isotherms, indicating that copper and zinc ions were easily adsorbed by NA with maximum adsorption capacities of 87.7 and 77.5 mg/g for Cu2+ and Zn2+, respectively. Thermodynamic parameters indicated that the adsorption of Cu2+ was spontaneous(G<0) and the adsorption of Zn2+ might not be spontaneous (G > 0) by NA. Graphical abstract á .
