Schistosomiasis vaccine discovery using immunomics

The recent publication of the Schistosoma japonicum and S. mansoni genomes has expanded greatly the opportunities for post-genomic schistosomiasis vaccine research. Immunomics protein microarrays provide an excellent application of this new schistosome sequence information, having been utilised successfully for vaccine antigen discovery with a range of bacterial and viral pathogens, and malaria

Elastic precursor of the transformation from glycolipid-nanotube to -vesicle

By the combination of optical tweezer manipulation and digital video microscopy, the flexural rigidity of single glycolipid "nano" tubes has been measured below the transition temperature at which the lipid tubules are transformed into vesicles. Consequently, we have found a clear reduction of the rigidity obviously before the transition as temperature increasing. Further experiments of infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC) have suggested a microscopic change of the tube walls, synchronizing with the precursory softening of the nanotubes.Comment: 9 pages, 6 figure

Sliding Columnar Phase of DNA-Lipid Complexes

We introduce a simple model for DNA-cationic-lipid complexes in which galleries between planar bilayer lipid lamellae contain DNA 2D smectic lattices that couple orientationally and positionally to lattices in neighboring galleries. We identify a new equilibrium phase in which there are long-range orientational but not positional correlations between DNA lattices. We discuss properties of this new phase such as its X-ray structure factor S(r), which exhibits unusual exp(- const.ln^2 r) behavior as a function of in-plane separation r.Comment: This file contains 4 pages of double column text and one postscript figure. This version includes interactions between dislocations in a given gallery and presents an improved estimate of the decoupling temperature. It is the published versio

Nonlinear Elasticity of the Sliding Columnar Phase

The sliding columnar phase is a new liquid-crystalline phase of matter composed of two-dimensional smectic lattices stacked one on top of the other. This phase is characterized by strong orientational but weak positional correlations between lattices in neighboring layers and a vanishing shear modulus for sliding lattices relative to each other. A simplified elasticity theory of the phase only allows intralayer fluctuations of the columns and has three important elastic constants: the compression, rotation, and bending moduli, $B$, $K_y$, and $K$. The rotationally invariant theory contains anharmonic terms that lead to long wavelength renormalizations of the elastic constants similar to the Grinstein-Pelcovits renormalization of the elastic constants in smectic liquid crystals. We calculate these renormalizations at the critical dimension $d=3$ and find that $K_y(q) \sim K^{1/2}(q) \sim B^{-1/3}(q) \sim (\ln(1/q))^{1/4}$, where $q$ is a wavenumber. The behavior of $B$, $K_y$, and $K$ in a model that includes fluctuations perpendicular to the layers is identical to that of the simple model with rigid layers. We use dimensional regularization rather than a hard-cutoff renormalization scheme because ambiguities arise in the one-loop integrals with a finite cutoff.Comment: This file contains 18 pages of double column text in REVTEX format and 6 postscript figure

The Influence of B Cell Depletion Therapy on Naturally Acquired Immunity to Streptococcus pneumoniae

The anti-CD20 antibody Rituximab to deplete CD20+ B cells is an effective treatment for rheumatoid arthritis and B cell malignancies, but is associated with an increased incidence of respiratory infections. Using mouse models we have investigated the consequences of B cell depletion on natural and acquired humoral immunity to Streptococcus pneumoniae. B cell depletion of naïve C57Bl/6 mice reduced natural IgM recognition of S. pneumoniae, but did not increase susceptibility to S. pneumoniae pneumonia. ELISA and flow cytometry assays demonstrated significantly reduced IgG and IgM recognition of S. pneumoniae in sera from mice treated with B cell depletion prior to S. pneumoniae nasopharyngeal colonization compared to untreated mice. Colonization induced antibody responses to protein rather than capsular antigen, and when measured using a protein array B cell depletion prior to colonization reduced serum levels of IgG to several protein antigens. However, B cell depleted S. pneumoniae colonized mice were still partially protected against both lung infection and septicemia when challenged with S. pneumoniae after reconstitution of their B cells. These data indicate that although B cell depletion markedly impairs antibody recognition of S. pneumoniae in colonized mice, some protective immunity is maintained, perhaps mediated by cellular immunity

Genetic Resistance to Malaria Is Associated With Greater Enhancement of Immunoglobulin (Ig)M Than IgG Responses to a Broad Array of Plasmodium falciparum Antigens

Background. People of the Fulani ethnic group are more resistant to malaria compared with genetically distinct ethnic groups, such as the Dogon people, in West Africa, and studies suggest that this resistance is mediated by enhanced antibody responses to Plasmodium falciparum antigens. However, prior studies measured antibody responses to <0.1% of P falciparum proteins, so whether the Fulani mount an enhanced and broadly reactive immunoglobulin (Ig)M and IgG response to P falciparum remains unknown. In general, little is known about the extent to which host genetics influence the overall antigen specificity of IgM and IgG responses to natural infections. Methods. In a cross-sectional study in Mali, we collected plasma from asymptomatic, age-matched Fulani (n = 24) and Dogon (n = 22) adults with or without concurrent P falciparum infection. We probed plasma against a protein microarray containing 1087 P falciparum antigens and compared IgM and IgG profiles by ethnicity. Results. We found that the breadth and magnitude of P falciparum-specific IgM and IgG responses were significantly higher in the malaria-resistant Fulani versus the malaria-susceptible Dogon, and, unexpectedly, P falciparum-specific IgM responses more strongly distinguished the 2 ethnic groups. Conclusions. These findings point to an underappreciated role for IgM in protection from malaria, and they suggest that host genetics may influence the antigen specificity of IgM and IgG responses to infection

Genomic Organization, Splice Variants and Expression of CGMl, a CD66-related Member of the Carcinoembryonic Antigen Gene Family

The tumor marker carcinoembryonic antigen (CEA) belongs to a family of proteins which are composed of one immunogiobulin variable domain and a varying number of immunoglobulin constant-like domains. Most of the membrane-bound members, which are anchored either by a glycosylphosphatidylinositol moiety or a transmembrane domain, have been shown to convey cell adhesion in vitro. Here we describe two splice variants of CGMI. a transmembrane member of the CEA family without immunoglobulin constant.like domains. CGM1a and CGM1c contain cytopiasmic domains of 71 and 31 amino acids, respectively, The cytoplasmic region of CGM1a is encoded by four exons (Cyt1-Cyt4). Differential splicing of the Cyt1 exon (53 bp)..

Structural Properties of the Sliding Columnar Phase in Layered Liquid Crystalline Systems

Under appropriate conditions, mixtures of cationic and neutral lipids and DNA in water condense into complexes in which DNA strands form local 2D smectic lattices intercalated between lipid bilayer membranes in a lamellar stack. These lamellar DNA-cationic-lipid complexes can in principle exhibit a variety of equilibrium phases, including a columnar phase in which parallel DNA strands from a 2D lattice, a nematic lamellar phase in which DNA strands align along a common direction but exhibit no long-range positional order, and a possible new intermediate phase, the sliding columnar (SC) phase, characterized by a vanishing shear modulus for relative displacement of DNA lattices but a nonvanishing modulus for compressing these lattices. We develop a model capable of describing all phases and transitions among them and use it to calculate structural properties of the sliding columnar phase. We calculate displacement and density correlation functions and x-ray scattering intensities in this phase and show, in particular, that density correlations within a layer have an unusual $\exp(- {\rm const.} \ln^2 r)$ dependence on separation r. We investigate the stability of the SC phase with respect to shear couplings leading to the columnar phase and dislocation unbinding leading to the lamellar nematic phase. For models with interactions only between nearest neighbor planes, we conclude that the SC phase is not thermodynamically stable. Correlation functions in the nematic lamellar phase, however, exhibit SC behavior over a range of length scalesComment: 28 pages, 4 figure

Protective Effect of Nasal Colonisation with ∆cps/piaA and ∆cps/proABCStreptococcus pneumoniae Strains against Recolonisation and Invasive Infection

RATIONALE: Nasopharyngeal administration of live virulence-attenuated Streptococcus pneumoniae strains is a potential novel preventative strategy. One target for creating reduced virulence S. pneumoniae strains is the capsule, but loss of the capsule reduces the duration of S. pneumoniae colonisation in mice which could impair protective efficacy against subsequent infection. OBJECTIVES: To assess protective efficacy of nasopharyngeal administration of unencapsulated S. pneumoniae strains in murine infection models. METHODS: Strains containing cps locus deletions combined with the S. pneumoniae virulence factors psaA (reduces colonisation) or proABC (no effect on colonisation) were constructed and their virulence phenotypes and ability to prevent recolonisation or invasive infection assessed using mouse infection models. Serological responses to colonisation were compared between strains using ELISAs, immunoblots and 254 S. pneumoniae protein antigen array. Measurements and Main Results: The ∆cps/piaA and ∆cps/proABC strains were strongly attenuated in virulence in both invasive infection models and had a reduced ability to colonise the nasopharynx. ELISAs, immunoblots and protein arrays showed colonisation with either strain stimulated weaker serological responses than the wild type strain. Mice previously colonised with these strains were protected against septicaemic pneumonia but, unlike mice colonised with the wild type strain, not against S. pneumoniae recolonisation. CONCLUSIONS: Colonisation with the ∆cps/piaA and ∆cps/proABC strains prevented subsequent septicaemia, but in contrast, to published data for encapsulated double mutant strains they did not prevent recolonisation with S. pneumoniae. These data suggest targeting the cps locus is a less effective option for creating live attenuated strains that prevent S. pneumoniae infections