Hepatitis C Virus Antigenic Convergence

Vaccine development against hepatitis C virus (HCV) is hindered by poor understanding of factors defining cross-immunoreactivity among heterogeneous epitopes. Using synthetic peptides and mouse immunization as a model, we conducted a quantitative analysis of cross-immunoreactivity among variants of the HCV hypervariable region 1 (HVR1). Analysis of 26,883 immunological reactions among pairs of peptides showed that the distribution of cross-immunoreactivity among HVR1 variants was skewed, with antibodies against a few variants reacting with all tested peptides. The HVR1 cross-immunoreactivity was accurately modeled based on amino acid sequence alone. The tested peptides were mapped in the HVR1 sequence space, which was visualized as a network of 11,319 sequences. The HVR1 variants with a greater network centrality showed a broader cross-immunoreactivity. The entire sequence space is explored by each HCV genotype and subtype. These findings indicate that HVR1 antigenic diversity is extensively convergent and effectively limited, suggesting significant implications for vaccine development

Photoinduced electron transfer between the interlocked components of porphyrin catenanes: effect of the presence of nonequivalent reduction sites on the charge recombination rate

Catenanes made up of several polyether-strapped porphyrin macrocycles interlinked with the cyclic electron acceptor cyclobis(paraquat-p-phenylene) were spectroscopically, photophysically, and electrochemically characterized. The catenanes exhibit very rich redox behavior due to the presence of several different and interacting electro-active subunits. The redox patterns represent useful fingerprints that provide detailed information on the electronic interactions and the chemical environments that the electroactive subunits experience in the supramolecular arrays. A photoinduced electron transfer from the porphyrin excited state (charge separation CS) occurs with ґ=20 ps in the catenanes with a larger strap and faster than 20 ps (instrumental resolution) in the catenanes with a shorter strap. The resulting charge-separated state recombines to the ground state (charge recombination CR) with lifetimes similar in all cases, 41±4 ps. Comparison of the electron transfer rates CS and CR in the host-guest complexes of the same porphyrins with the noncyclic electron acceptor paraquat, indicate slower reactions in the [2]catenanes. This behavior is assigned to the different separation between reacting partners determined by the type of bond (weak interaction or mechanical) and to a two-step consecutive electron transfer to different sites of the macrocyclic electron acceptor in the catenanes which retards charge recombination

Photoinduced electron transfer between the interlocked components of porphyrin catenanes: Effect of the presence of nonequivalent reduction sites on the charge recombination rate

Weinheim, German

Photocatalytic Water Oxidation: Tuning Light-Induced Electron Transfer by Molecular Co4O4Cores

Isostructural cubane-shaped catalysts [CoIII 4(\u3bc-O)4(\u3bc-CH3COO)4(p-NC5H4X)4], 1-X (X = H, Me, t-Bu, OMe, Br, COOMe, CN), enable water oxidation under dark and illuminated conditions, where the primary step of photoinduced electron transfer obeys to Hammett linear free energy relationship behavior. Ligand design and catalyst optimization are instrumental for sustained O2 productivity with quantum efficiency up to 80% at \u3bb > 400 nm, thus opening a new perspective for in vitro molecular photosynthesi

Working the other way around: Photocatalytic water oxidation triggered by reductive quenching of the photoexcited chromophore

A detailed photophysical investigation of the photocatalytic water oxidation system based on the tetraruthenium polyoxometalate [Ru₄(μ-O)₄(μ–OH)₂(H₂O)₄(γ-SiW₁₀O₃₆)₂]^10– (<b>1</b>) as the catalyst, the tetranuclear ruthenium dendrimer [Ru­{(μ-2,3-dpp)­Ru­(bpy)₂}₃]⁸⁺ (<b>2</b>) as the light-harvesting photosensitizer, and persulfate (S₂O₈^2–) as the sacrificial electron acceptor has shown that the water oxidation mechanism proceeds through an unusual, “anti-biomimetic” pathway: The first photochemical event is indeed a reductive quenching of the excited photosensitizer by the catalyst, followed by electron scavenging by the sacrificial electron acceptor, both occurring on the picosecond time scale within ion-paired species. As an unprecedented photoreaction mechanism for molecular water oxidation systems, these results suggest a new way to combine photosensitizers and catalysts, taking advantage of suitable chemical interactions and alternative photoinduced processes for the construction of efficient water-splitting devices

Antigenicity and Immunogenicity of Novel Chimeric Hepatitis B Surface Antigen Particles with Exposed Hepatitis C Virus Epitopes

The small envelope protein of hepatitis B virus (HBsAg-S) can self-assemble into highly organized virus like particles (VLPs) and induce an effective immune response. In this study, a restriction enzyme site was engineered into the cDNA of HBsAg-S at a position corresponding to the exposed site within the hydrophilic a determinant region (amino acid [aa] 127–128) to create a novel HBsAg vaccine vector allowing surface orientation of the inserted sequence. We inserted sequences of various lengths from hypervariable region 1 (HVR1) of the hepatitis C virus (HCV) E2 protein containing immunodominant epitopes and demonstrated secretion of the recombinant HBsAg VLPs from transfected mammalian cells. A number of different recombinant proteins were synthesized, and HBsAg VLPs containing inserts up to 36 aa were secreted with an efficiency similar to that of wild-type HBsAg. The HVR1 region exposed on the particles retained an antigenic structure similar to that recognized immunologically during natural infection. VLPs containing epitopes from either HCV-1a or -1b strains were produced that induced strain-specific antibody responses in immunized mice. Injection of a combination of these VLPs induced antibodies against both HVR1 epitopes that resulted in higher titers than were achieved by vaccination with the individual VLPs, suggesting a synergistic effect. This may lead to the development of recombinant particles which are able to induce a broad anti-HCV immune response against the HCV quasispecies or other quasispecies-like infectious agents