CD1b presents self and Borrelia burgdorferi diacylglycerols to human T cells.

Lyme disease is a common multisystem disease caused by infection with a tick-transmitted spirochete, Borrelia burgdorferi and related Borrelia species. The monoglycosylated diacylglycerol known as B. burgdorferi glycolipid II (BbGL-II) is a major target of antibodies in sera from infected individuals.

A T-cell receptor escape channel allows broad T-cell response to CD1b and membrane phospholipids.

CD1 proteins are expressed on dendritic cells, where they display lipid antigens to T-cell receptors (TCRs). Here we describe T-cell autoreactivity towards ubiquitous human membrane phospholipids presented by CD1b. These T-cells discriminate between two major types of lipids, sphingolipids and phospholipids, but were broadly cross-reactive towards diverse phospholipids including phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine.

Vaccination with Shigella flexneri 2a conjugate induces type 2a and cross-reactive type 6 antibodies in humans but not in mice.

Shigella flexneri (S. flexneri) 6 has emerged as an important cause of shigellosis. Our efficacy study of Shigella sonnei and S.

Bacillus anthracis Capsular Conjugates Elicit Chimpanzee Polyclonal Antibodies That Protect Mice from Pulmonary Anthrax.

The immunogenicity of Bacillus anthracis capsule (poly-γ-D-glutamic acid [PGA]) conjugated to recombinant B. anthracis protective antigen (rPA) or to tetanus toxoid (TT) was evaluated in two anthrax-naive juvenile chimpanzees. In a previous study of these conjugates, highly protective monoclonal antibodies (MAbs) against PGA were generated.

Toward a new vaccine for pertussis.

To overcome the limitations of the current pertussis vaccines, those of limited duration of action and failure to induce direct killing of Bordetella pertussis, a synthetic scheme was devised for preparing a conjugate vaccine composed of the Bordetella bronchiseptica core oligosaccharide with one terminal trisaccharide to aminooxylated BSA via their terminal ketodeoxyoctanate residues. Conjugate-induced antibodies, by a fraction of an estimated human dose injected into young outbred mice as a saline solution, were bactericidal against B. pertussis, and their titers correlated with their ELISA values.

Bacillus anthracis cell wall peptidoglycan but not lethal or edema toxins produces changes consistent with disseminated intravascular coagulation in a rat model.

Background: Disseminated intravascular coagulation (DIC) appears to be important in the pathogenesis of Bacillus anthracis infection, but its causes are unclear. Although lethal toxin (LT) and edema toxin (ET) could contribute, B. anthracis cell wall peptidoglycan (PGN), not the toxins, stimulates inflammatory responses associated with DIC.

Reinvestigation of the structure of Brucella O-antigens.

O-Specific polysaccharides of Brucella contain two antigenic determinants, called A and M. Most of the strains express epitope A with a small amount of epitope M, whereas Brucella melitensis strain 16 M expresses longer polymer consisting mostly of M-type epitopes. Proposed explanation was that epitope A is defined by 1-2-linked homopolymer of N-formylperosamine (Rha4NFo), while epitope M is a pentasaccharide with four 2- and one 3-substituted Rha4NFo.

The capsular polysaccharide and lipopolysaccharide structures of two carbapenem resistant Klebsiella pneumoniae outbreak isolates.

Carbapenem resistant Klebsiella pneumoniae (CRKP) are isolated with increasing frequency, especially from immunocompromized patients. The capsular polysaccharide (CPS) types of CPKP were not determined. Investigation of two CRKP isolates from a 2011 outbreak at the Clinical Center, the National Institutes of Health, identified a new capsular type shared by the two isolates, similar to K.

The study of the core part and non-repeating elements of the O-antigen of Brucella lipopolysaccharide.

Brucella is an animal and human pathogen that expresses several virulence factors required for host cell invasion and intracellular survival. It produces LPS with unusually low toxicity, which hampers the detection of bacteria by the host immune system and thus provides resistance against intracellular antimicrobial mechanisms of the host. By chemical and spectroscopic methods we determined the structure of the LPS core and of a non-repetitive oligosaccharide fragment at the reducing end of the O-specific polysaccharide.

Identification of the methyl phosphate substituent at the non-reducing terminal mannose residue of the O-specific polysaccharides of Klebsiella pneumoniae O3, Hafnia alvei PCM 1223 and Escherichia coli O9/O9a LPS.

O-specific polysaccharides of Gram-negative bacteria are synthesized by two different mechanisms: polymerization of the pre-formed O-repeating unit or sequential addition of the monosaccharides to the growing polysaccharide chain. In the second case, growth of the polymer can be further subdivided into two groups depending on the presence or absence of a special monosaccharide or non-sugar substituent that terminates the glycan. A family of polymannose O-polysaccharides provides prototypes for the chain terminating process.

Conjugation of LPS-derived oligosaccharides to proteins using oxime chemistry.

Conjugates of bacterial polysaccharides covalently bound to a carrier protein are among licensed human vaccines. Immunization of adults and children with these vaccines results in induction of saccharide-specific antibodies composed mainly of the IgG class. Depending on the choice of coupling technique, saccharides can be attached to a protein by either multiple- or single-point attachments.

Oligosaccharide conjugates of Bordetella pertussis and bronchiseptica induce bactericidal antibodies, an addition to pertussis vaccine.

Pertussis is a highly contagious respiratory disease that is especially dangerous for infants and children. Despite mass vaccination, reported pertussis cases have increased in the United States and other parts of the world, probably because of increased awareness, improved diagnostic means, and waning vaccine-induced immunity among adolescents and adults. Licensed vaccines do not kill the organism directly; the addition of a component inducing bactericidal antibodies would improve vaccine efficacy.

Pre- and postexposure protection against virulent anthrax infection in mice by humanized monoclonal antibodies to Bacillus anthracis capsule.

One of the two essential virulence factors of Bacillus anthracis is the poly-γ-D-glutamic acid (γDPGA) capsule. Five γDPGA-specific antibody antigen-binding fragments (Fabs) were generated from immunized chimpanzees. The two selected for further study, Fabs 11D and 4C, were both converted into full-length IgG1 and IgG3 mAbs having human IgG1 or IgG3 constant regions.

The structure of the Escherichia coli O148 lipopolysaccharide core region and its linkage to the O-specific polysaccharide.

Recently it was demonstrated that Shigella dysenteriae type 1, a cause of severe dysentery epidemics, gained its O-specific polysaccharide (O-SP) from Escherichia coli O148. The O-SPs of these bacteria differ only by a galactose residue in the repeat unit of S. dysenteriae type 1 in place of a glucose residue in E.

Immunochemical studies of Shigella flexneri 2a and 6, and Shigella dysenteriae type 1 O-specific polysaccharide-core fragments and their protein conjugates as vaccine candidates.

There is no licensed vaccine for the prevention of shigellosis. Our approach to the development of a Shigella vaccines is based on inducing serum IgG antibodies to the O-specific polysaccharide (O-SP) domain of their lipopolysaccharides (LPS). We have shown that low molecular mass O-SP-core (O-SPC) fragments isolated from Shigella sonnei LPS conjugated to proteins induced significantly higher antibody levels in mice than the full length O-SP conjugates.

A bicomponent Plasmodium falciparum investigational vaccine composed of protein-peptide conjugates.

There is yet no licensed vaccine against malaria, a serious human disease affecting mostly children, with an annual death rate of about one million. Plasmodia, the malaria-causing parasites, have two obligatory hosts: mammals or birds, in which they multiply asexually, and mosquitoes with sexual multiplication. The most common and serious type of malaria is caused by Plasmodium falciparum.

Immunogenic and adjuvant properties of Haemophilus ducreyi lipooligosaccharides.

Haemophilus ducreyi, the chancroid-causing bacterium, produces lipooligosaccharides (HdLOS) that comprise 5-11 partially sialylated monosaccharides. Subcutaneous immunisation of mice with 5 microg of HdLOS purified from H. ducreyi strains 4438 and 7470 induced high levels of anti-HdLOS IgG.

Synthesis, characterization, and immunogenicity in mice of Shigella sonnei O-specific oligosaccharide-core-protein conjugates.

Shigellosis, an enteric disease, is on the World Health Organization's priority prevention list. In one study, the Shigella sonnei O-specific polysaccharide (O-SP)-protein conjugate showed 72% protection against disease in Israeli army recruits exposed to high rates (8-14%) of infection. The protection was related to vaccine-induced IgG anti-O-SP levels.

Pertussis vaccine: a critique.

A critical level of serum IgG pertussis toxin antibody is both essential and sufficient to confer individual and herd immunity to pertussis. Monocomponent pertussis toxoid conferred such immunity in Sweden and in Denmark. We refute the notion that filamentous hemagglutinin, pertactin, and fimbriae add to the immunity conferred by pertussis toxoid and describe the artifact created when efficacy is estimated for multicomponent pertussis vaccines.

The elucidation of the structure of the core part of the LPS from Plesiomonas shigelloides serotype O17 expressing O-polysaccharide chain identical to the Shigella sonnei O-chain.

Plesiomonas shigelloides O17 LPS contains the same O-antigenic polysaccharide chain as a causative agent of dysentery, Shigella sonnei. This polysaccharide can be used as a component of a vaccine against dysentery. Core part of the P.

The structure of the carbohydrate backbone of the LPS from Shewanella spp. MR-4.

The rough type lipopolysaccharide isolated from Shewanella spp. strain MR-4 was analyzed using NMR, mass spectroscopy, and chemical methods. Two structural variants have been found, both contained 8-amino-3,8-dideoxy-d-manno-octulosonic acid and lacked L-glycero-D-manno-heptose.

Saccharides cross-reactive with Bacillus anthracis spore glycoprotein as an anthrax vaccine component.

Bacillus anthracis is a spore-forming bacterium that causes anthrax in humans and in other mammals. The glycoprotein BclA (Bacillus collagen-like protein of anthracis) is a major constituent of the exosporium, the outermost surface of B. anthracis spores.

Saccharide/protein conjugate vaccines for Bordetella species: preparation of saccharide, development of new conjugation procedures, and physico-chemical and immunological characterization of the conjugates.

Bordetellae are Gram-negative bacilli causing respiratory tract infections of mammals and birds. Clinically important are B. pertussis, B.