Author response to letter to the editor by Marciani et al.
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Adjuvants, Immunologic↗
Biomedical subjects
Gui Liu
Publications and source records attributed to Gui Liu.
Immunization with a mycobacterial lipid vaccine improves pulmonary pathology in the guinea pig model of tuberculosis.
Lipids and glycolipid molecules derived from Mycobacterium tuberculosis can be presented to T cells by CD1 cell-surface molecules in humans. These lipid-specific T cells are cytolytic, secrete pro-inflammatory cytokines and have bactericidal activity. Here, we describe studies in which lipids from M. tuberculosis were incorporated into liposomes with adjuvant and tested as vaccines in a guinea pig aerosol tuberculosis challenge model. Animals vaccinated with mycobacterial lipids showed reduced bacterial burdens in the lung and spleen at 4 weeks after infection. In addition, the lungs of lipid-vaccinated animals also had significantly less pathology, with granulomatous lesions being smaller and more lymphocytic. In contrast, animals receiving only vehicle control immunizations had granulomatous lesions that were larger and often contained caseous necrotic centers. Quantification of histopathology by morphometric analysis revealed that the overall percentage of lung occupied by diseased tissue was significantly smaller in lipid-vaccinated animals as compared to vehicle control animals. In addition, the mean area of individual granulomatous lesions was found to be significantly smaller in both lipid- and bacillus Calmette-Guerin-vaccinated guinea pigs. These data support an important role for lipid antigens in the immune response to M. tuberculosis infection, potentially through the generation of CD1-restricted T cells. Immunogenic lipids thus represent a novel class of antigens that might be included to enhance the protective effects of subunit vaccine formulations.
Adjuvants, Immunologic↗
QS-21 structure/function studies: effect of acylation on adjuvant activity.
QS-21 is a natural saponin adjuvant derived from the tree Quillaja saponaria Molina. Previous studies over a limited dose range suggested the acylation is critical to adjuvant activity. In this study, we prepared DS-1 (deacylated QS-21) and RDS-1 (reacylated DS-1 with dodecylamine at a different site than QS-21) to determine the effect on a dose-response curve over a wider range in mice. DS-1 and RDS-1 induced IgG1 responses at higher doses compared to that induced by QS-21. DS-1 was inactive for inducing IgG2a or CTL responses at any doses. RDS-1 showed moderate IgG2a response at 240 microg, but did not show CTL response at any dose evaluated.
Acylation↗
Photochemistry of a Trisilane Substituted by a Pendant p-Cyanostilbene Electron Acceptor Chromophore.
Photolysis of (E)-4-cyano-4'-(2-heptamethyltrisilanyl)stilbene (E)-3 in a medium polarity solvent (CH(2)Cl(2)) results in efficient intramolecular electron transfer, which converts the initial pi,pi excited state ((1)LE state) to the charge transfer (CT) excited state. The CT excited state fluorescesces, undergoes E,Z photoisomerization, and reacts with MeOH to produce hydrosilane 4 via Si-Si bond cleavage and protonation of the central silicon, as shown by deuterium labeling. The CT excited state assignments are consistent with the observed quadratic plots of 1/Phi(f) versus [MeOH] and 1/Phi(EZ)() versus [MeOH], which indicate that both the initial (1)LE state and the CT excited state are quenched by MeOH, with the CT excited state serving as the emissive state and the state primarily responsible for the E,Z photoisomerization. Although biacetyl triplet sensitized photolysis results in efficient E,Z isomerization, quenching of direct photolyses by azulene shows (Z)-3 is not a product of the lowest energy triplet excited state, populated from the CT state by back electron transfer. The azulene quenching also shows that hydrosilane 4 is formed from the same excited state that gives (Z)-3. The intermediacy of a complex of the CT excited state with MeOH accounts for the observed upward curvature in the plot of 1/Phi(SiH) vs 1/[MeOH]. The linear behavior of Phi(EZ)()/Phi(SiH) x [MeOH] versus 1/[MeOH] further suggests that this complex reacts with uncomplexed MeOH to give hydrosilane 4.
Journal Article↗