bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity and Efficacy inAotusMonkeys of Four RecombinantPlasmodium falciparumVaccines in Multiple Adjuvant Formulations Based on the 19-Kilodalton C Terminus of Merozoite Surface Protein 1
Authors: Kumar Sanjai , Collins William , Egan Andrea , Yadava Anjali , Garraud Olivier , Blackman Michael J. , Patino Jose A. Guevara , Diggs Carter , Kaslow David C. 
Published: July 2002

ABSTRACTThe immunogenicity and protective efficacy of four versions of recombinant C-terminal 19-kDa epidermal growth factor-like region of the major surface protein 1 (rMSP119) ofPlasmodium falciparumwas studied inAotusmonkeys. Vaccination with each of the four rMSP119constructs elicited high levels of antibodies to MSP119but only one construct, the 19-kDa fragment expressed as a secreted fusion protein fromSaccharomyces cerevisiae(yP30P2MSP119), induced a high degree of protective immunity inAotus nancymaiagainst lethalP. falciparumchallenge. Protective formulation required Freund's adjuvant; vaccination with yP30P2MSP119in six other adjuvants that are suitable for human use induced lower levels of antibody response and no protection. These results emphasize the need to continue the search for an adjuvant that is comparable to Freund's adjuvant in potency and is safe for use in humans.
Interaction of HLA and Age on Levels of Antibody toPlasmodium falciparumRhoptry-Associated Proteins 1 and 2
Authors: Johnson Armead , Leke Rose , Harun Lucy , Ginsberg Christina , Ngogang Jeanne , Stowers Anthony , Saul Allan , Quakyi Isabella A. 
Published: July 2002

ABSTRACTThePlasmodium falciparumrhoptry-associated proteins 1 and 2 (RAP1 and RAP2) are candidate antigens for a subunit malaria vaccine. The design of the study, which looks at the acquisition of immunity to malaria from childhood to old age, has allowed us to document the interaction of HLA and age on levels of antibody to specific malarial antigens. Antibodies reach maximum levels to RAP1 after the age of 15 but to RAP2 only after the age of 30. The effect of HLA-DRB1 and -DQB1 and age on levels of antibody to rRAP1 and rRAP2 was analyzed with a multiple regression model in which all HLA alleles and age were independent variables. DQB1*0301 and -*03032 showed an age-dependent association with levels of antibody to rRAP1, being significant in children 5 to 15 years (P< 0.001) but not in individuals over 15 years of age. DRB1*03011 showed an age-dependent association with antibody levels to rRAP2; however, this association was in adults over the age of 30 years (P< 0.01) but not in individuals under the age of 30 years. No associations were detected between DRB1 alleles and RAP1 antibody levels or between DQB1 alleles and RAP2 antibody levels. Thus, not only the HLA allele but also the age at which an interaction is manifested varies for different malarial antigens. The interaction may influence either the rate of acquisition of antibody or the final level of antibody acquired by adults.
Adhesion of
Aspergillus
Species to Extracellular Matrix Proteins: Evidence for Involvement of Negatively Charged Carbohydrates on the Conidial Surface
Authors: Wasylnka Julie A. , Moore Margo M. 
Published: July 2002

ABSTRACT

Invasive lung disease caused by
Aspergillus
species is a potentially fatal infection in immunocompromised patients. The adhesion of
Aspergillus fumigatus
conidia to proteins in the basal lamina is thought to be an initial step in the development of invasive aspergillosis. The purpose of this study was to determine the mechanism of adhesion of
A. fumigatus
conidiospores to basal-lamina proteins and to determine whether conidia possess unique adhesins which allow them to colonize the host. We compared conidia from different
Aspergillus
species for the ability to bind to purified fibronectin and intact basal lamina. Adhesion assays using immobilized fibronectin or type II pneumocyte-derived basal lamina showed that
A. fumigatus
conidia bound significantly better than those of other
Aspergillus
species to both fibronectin and intact basal lamina. Neither desialylation nor complete deglycosylation of fibronectin decreased the binding of
A. fumigatus
conidia to fibronectin, suggesting that oligosaccharides on fibronectin were not involved in conidiospore binding. Further evidence for this hypothesis came from experiments using purified fragments of fibronectin;
A. fumigatus
conidia preferentially bound to the nonglycosylated 40-kDa fragment which contains the glycosaminoglycan (GAG) binding domain. Negatively charged carbohydrates, including dextran sulfate and heparin, as well as high-ionic-strength buffers, inhibited binding of
A. fumigatus
conidia to both fibronectin and intact basal lamina, suggesting that negatively charged carbohydrates on the surface of the conidium may bind to the GAG binding domain of fibronectin and other basal-lamina proteins. These data provide evidence for a novel mechanism of conidial attachment whereby adherence to fibronectin and other basal-lamina proteins is mediated via negatively charged carbohydrates on the conidial surface.
Bacterial Cell Wall-Induced Arthritis: Chemical Composition and Tissue Distribution of FourLactobacillusStrains
Authors: Šimelyte Egle , Rimpiläinen Marja , Lehtonen Leena , Zhang Xiang , Toivanen Paavo 
Published: July 2002

ABSTRACTTo study what determines the arthritogenicity of bacterial cell walls, cell wall-induced arthritis in the rat was applied, using four strains ofLactobacillus. Three of the strains used proved to induce chronic arthritis in the rat; all wereLactobacillus casei. The cell wall ofLactobacillus fermentumdid not induce chronic arthritis. All arthritogenic bacterial cell walls had the same peptidoglycan structure, whereas that ofL. fermentumwas different. Likewise, all arthritogenic cell walls were resistant to lysozyme degradation, whereas theL. fermentumcell wall was lysozyme sensitive. Muramic acid was observed in the liver, spleen, and lymph nodes in considerably larger amounts after injection of an arthritogenicL. caseicell wall than following injection of a nonarthritogenicL. fermentumcell wall. TheL. caseicell wall also persisted in the tissues longer than theL. fermentumcell wall. The present results, taken together with those published previously, underline the possibility that the chemical structure of peptidoglycan is important in determining the arthritogenicity of the bacterial cell wall.
Role of Phosphoglucomutase of
Bordetella bronchiseptica
in Lipopolysaccharide Biosynthesis and Virulence
Authors: West Nicholas P. , Jungnitz Heidrun , Fitter John T. , McArthur Jason D. , Guzmán Carlos A. , Walker Mark J. 
Published: July 2002

ABSTRACT

The phosphoglucomutase (PGM)-encoding gene of
Bordetella bronchiseptica
is required for lipopolysaccharide (LPS) biosynthesis. An insertion mutant of the wild-type
B. bronchiseptica
strain BB7865 which disrupted LPS biosynthesis was created and characterized (BB7865
pgm
). Genetic analysis of the mutated gene showed it shares high identity with PGM genes of various bacterial species and forms part of an operon which also encompasses the gene encoding phosphoglucose isomerase. Functional assays for PGM revealed that enzyme activity is expressed in both
bvg
-positive and
bvg
-negative strains of
B. bronchiseptica
and is substantially reduced in BB7865
pgm
. Complementation of the mutated PGM gene with that from BB7865 restored the wild-type condition for all phenotypes tested. The ability of the mutant BB7865
pgm
to survive within J774.A1 cells was significantly reduced at 2 h (40% reduction) and 24 h (56% reduction) postinfection. BB7865
pgm
was also significantly attenuated in its ability to survive in vivo following intranasal infection of mice, being effectively cleared from the lungs within 4 days, whereas the wild-type strain persisted at least 35 days. The activities of superoxide dismutase, urease, and acid phosphatase were unaffected in the PGM-deficient strain. In contrast, the inability to produce wild-type LPS resulted in a reduced bacterial resistance to oxidative stress and a higher susceptibility to the antimicrobial peptide cecropin P.
Failure To Detect Muramic Acid in Normal Rat Tissues but Detection in Cerebrospinal Fluids from Patients with Pneumococcal Meningitis
Authors: Kozar Michael P. , Krahmer Mark T. , Fox Alvin , Gray Barry M. 
Published: July 2002

ABSTRACT
Muramic acid serves as a marker for the presence of bacterial cell wall debris in mammalian tissues. There have been a number of controversial and sometimes conflicting results on assessing the levels of muramic acid in health and disease. The present report is the first to use the state-of-the art technique, gas chromatography-tandem mass spectrometry, to identify and quantify the levels of muramic acid in tissues. Muramic acid was not found in normal rat brain or spleen. However, when tissues were spiked with muramic acid, it was readily identified. The detection limit was <1 ng of muramic acid/100 mg (wet weight) of tissue. The levels of muramic acid reported in diseased human spleen and spleen of arthritic rats, previously injected with bacterial cell walls, were 100- to 1,000-fold higher. In the present study, muramic acid was also readily detected in the cerebrospinal fluid of patients with pneumococcal meningitis (6.8 to 3,900 ng of muramic acid/ml of cerebrospinal fluid). In summary, there can be an enormous difference in the levels of muramic acid found in different mammalian tissues and body fluids in health and disease. This report could have great impact in future studies assessing the role of bacterial cell wall remnants in the pathogenesis of certain human inflammatory diseases.
Decorin-Binding Protein A (DbpA) of
Borrelia burgdorferi
Is Not Protective When Immunized Mice Are Challenged via Tick Infestation and Correlates with the Lack of DbpA Expression by
B. burgdorferi
in Ticks
Authors: Hagman Kayla E. , Yang Xiaofeng , Wikel Stephen K. , Schoeler George B. , Caimano Melissa J. , Radolf Justin D. , Norgard Michael V. 
Published: July 2002

ABSTRACT

Previous studies showed that decorin-binding protein A (DbpA) of
Borrelia burgdorferi
was a protective immunogen in the murine model of Lyme borreliosis when mice were challenged (needle inoculated) intradermally with in vitro-cultivated spirochetes. In the present study, DbpA-immunized C3H/HeJ mice were not protected from infection when infested with
Ixodes scapularis
nymphs harboring virulent
B. burgdorferi
297. This lack of protection correlated with the failure to detect DbpA on
B. burgdorferi
in ticks, suggesting that DbpA is not available as a target for bactericidal antibodies in serum when
B. burgdorferi
-infected ticks take their blood meal from an immunized host. The failure of DbpA immunization to protect tick-challenged mice contradicts the results of earlier needle inoculation vaccination experiments and suggests that DbpA may not be suitable as a Lyme disease vaccine.
Protective Immunity against Congenital Toxoplasmosis with Recombinant SAG1 Protein in a Guinea Pig Model
Authors: Haumont Michèle , Delhaye Louis , Garcia Lida , Jurado Margarita , Mazzu Pasqualina , Daminet Véronique , Verlant Vincent , Bollen Alex , Biemans Ralph , Jacquet Alain 
Published: July 2002

ABSTRACTPrimary infection withToxoplasma gondiiduring pregnancy can induce fetal pathology and abortion in both humans and animals. The present study describes the development of an experimental model of congenital toxoplasmosis in the guinea pig. In this animal model, we evaluated the protective effect of vaccination with a recombinant form of SAG1 against maternofetal transmission of tachyzoites. The presence of parasites in fetuses was determined by nested PCRs and by an in vivo readout after fetal brain homogenate injections in mice. The absence of parasites was demonstrated in 66 to 86% of fetuses derived from adult guinea pigs immunized with SAG1 and challenged with the mildly virulentT. gondiistrain C56. In contrast, more than 80% of fetuses from mock-immunized guinea pigs were infected. The protection was not correlated with titers of antibody to SAG1. Our results indicated that this experimental model constitutes a relevant model for evaluation of vaccine candidates against congenital toxoplasmosis and that SAG1 elicits significant protection against maternofetal transmission.
Toxoids of Streptococcal Pyrogenic Exotoxin A Are Protective in Rabbit Models of Streptococcal Toxic Shock Syndrome
Authors: Roggiani Manuela , Stoehr Jennifer A. , Olmsted Stephen B. , Matsuka Yury V. , Pillai Subramonia , Ohlendorf Douglas H. , Schlievert Patrick M. 
Published: July 2002

ABSTRACTStreptococcal pyrogenic exotoxins (SPEs) are superantigens that have been implicated in causing streptococcal toxic shock syndrome (STSS). Most notably, SPE serotype A is made by nearly all M-protein serotype 1 and 3 streptococci, the M types most associated with the illness (these strains contain one or more other SPEs, and those proteins are likely also to contribute to disease). We have prepared double-, triple-, and hexa-amino-acid mutants of SPE A by PCR and other mutagenesis procedures. The sites chosen for mutation were solvent-exposed residues thought to be important for T-cell receptor (TCR) or major histocompatibility complex (MHC) class II interaction. These mutants were nonsuperantigenic for human peripheral blood mononuclear cells and rabbit and mouse splenocytes and were nonlethal in two rabbit models of STSS. In addition, these mutants stimulated protective antibody responses. Interestingly, mutants that altered toxin binding to MHC class II were more immunogenic than mutants altering TCR binding. Collectively, these studies indicate that multiple-site mutants of SPE A are toxoids that may have use in protecting against the toxin's effects in STSS.
Silencing and Reactivation of Urease in
Yersinia pestis
Is Determined by One G Residue at a Specific Position in the
ureD
Gene
Authors: Sebbane Florent , Devalckenaere Annie , Foulon Jeannine , Carniel Elisabeth , Simonet Michel 
Published: July 2002

ABSTRACT

Yersinia pestis
, the plague agent, is a naturally nonureolytic microorganism, while all other
Yersinia
species display a potent urease activity. In this report we demonstrate that
Y. pestis
harbors a complete urease locus composed of three structural (
ureABC
) and four accessory (
ureEFGD
) genes. Absence of ureolytic activity is due to the presence of one additional G residue in a poly(G) stretch, which introduces a premature stop codon in
ureD
. The presence of the same additional G in eight other
Y. pestis
isolates indicates that this mutation is species specific. Spontaneous excision of the extra G occurs at a frequency of 10
−4
to 10
−5
and restores a ureolytic phenotype to
Y. pestis
. The virulence of two independent ureolytic clones of
Y. pestis
injected either intravenously, subcutaneously, or intragastrically did not differ from that of the parental strain in the mouse infection model. Coinfection experiments with an equal number of ureolytic and nonureolytic bacteria did not evidence any difference in the ability of the two variants to multiply in vivo and to cause a lethal infection. Altogether our results demonstrate that variation of one extra G residue in
ureD
determines the ureolytic activity of
Y. pestis
but does not affect its virulence for mice or its ability to multiply and disseminate.
Dual Role of theLeishmania majorRibosomal Protein S3a Homologue in Regulation of T- and B-Cell Activation
Authors: Cordeiro-da-Silva Anabela , Borges Margarida Coutinho , Guilvard Eliane , Ouaissi Ali 
Published: July 2002

ABSTRACTWe have recently characterized a novelLeishmania majorgene encoding a polypeptide of 30 kDa that was homologous to mammalian ribosomal protein S3a and was named LmS3a-related protein (LmS3arp). The protein was found to be expressed by all theLeishmaniaspecies so far examined (L. infantum, L. amazonensis, andL. mexicana). In the present study we have extended our approach to the analysis of LmS3arp activity on T- and B-cell functions in a murine model. The results presented in this report show that LmS3arp plays a dual role in the regulation of T- and B-cell reactivity. Indeed, we found that injection of the LmS3arp recombinant protein (rLmS3arp) into BALB/c mice induces preferential activation of B cells, as shown by the following criteria: (i) increased expression of CD69 molecules on immunoglobulin M (IgM)-secreting spleen cells, (ii) a considerable increase of IgM-secreting B cells, and (iii) elevated levels of IgM antibodies in the sera of injected animals. Moreover, the IgM antibodies are not specific to theLeishmaniaantigens but preferentially recognize heterologous antigens like myosin, thyroglobulin, DNA, and keyhole limpet hemocyanin. Furthermore, the strong polyclonal expansion of nonspecific, non-parasite-directed B-cell clones induced by rLmS3arp is concomitant with a marked inhibition of T-cell proliferation. Analysis of cytokine production revealed a significant downregulation of gamma interferon, interleukin-2 (IL-2), and IL-12 secretion. Taken together, our data suggest that rLmS3arp, through direct or indirect action toward B and T cells and cytokine secretion, could participate in the immunoregulatory processes that play a role in the balance of the Th1 and Th2 immune response.
agrExpression Precedes Escape of InternalizedStaphylococcus aureusfrom the Host Endosome
Authors: Qazi Saara N. A. , Counil Emilie , Morrissey Julie , Rees Catherine E. D. , Cockayne Alan , Winzer Klaus , Chan Weng C. , Williams Paul , Hill Philip J. 
Published: July 2002

ABSTRACTStaphylococcus aureusis a versatile pathogen capable of causing life-threatening infections. Many of its cell wall and exoproduct virulence determinants are controlled via the accessory gene regulator (agr). Although considered primarily as an extracellular pathogen, it is now recognized thatS. aureuscan be internalized by epithelial and endothelial cells. Traditional experimental approaches to investigate bacterial internalization are extremely time-consuming and notoriously irreproducible. We present here a new reporter gene method to assess intracellular growth ofS. aureusin MAC-T cells that utilizes agfp-luxABCDEreporter operon under the control of theBacillus megateriumxylApromoter, which inS. aureusis expressed in a growth-dependent manner. This facilitates assessment of the growth of internalized bacteria in a nondestructive assay. The dualgfp-luxreporter cassette was also evaluated as a reporter ofagrexpression and used to monitor the temporal induction ofagrduring the MAC-T internalization process. The data obtained suggest thatagrinduction occurs prior to endosomal lysis and thatagr-regulated exoproteins appear to be required prior to the release and replication ofS. aureuswithin the infected MAC-T cells.
Characterization of Antiapoptotic Activities ofChlamydia pneumoniaein Human Cells
Authors: Fischer Silke F. , Schwarz Claudia , Vier Juliane , Häcker Georg 
Published: July 2002

ABSTRACTChlamydia pneumoniaeis an obligate intracellular bacterium which frequently causes airway infection in humans and has been implicated in atherosclerosis. Here we show that infection withC. pneumoniaeprotects HeLa human epithelioid cells against apoptosis induced by external stimuli. In infected HeLa cells, apoptosis induced by staurosporine and CD95-death-receptor signaling was strongly reduced. Upon treatment with staurosporine, generation of effector caspase activity, processing of caspase-3 and caspase-9 and cytochromecredistribution were all profoundly inhibited in cells infected withC. pneumoniae. Bacterial protein synthesis during early infection was required for this inhibition. Furthermore, cytochromec-induced processing and activation of caspases were inhibited in cytosolic extracts from infected cells, suggesting that aC. pneumoniae-dependent antiapoptotic factor was generated in the cytosol upon infection. Infection withC. pneumoniaefailed to induce significant NF-κB activation in HeLa cells, indicating that no NF-κB-dependent cellular factors were involved in the protection against apoptosis. These results show thatC. pneumoniaeis capable of interfering with the host cell's apoptotic apparatus at probably at least two steps in signal transduction and might explain the propensity of these bacteria to cause chronic infections in humans.
Cure ofHelicobacter pyloriInfection and Resolution of Gastritis by Adoptive Transfer of Splenocytes in Mice
Authors: Eaton Kathryn A. , Mefford Megan E. 
Published: July 2002

ABSTRACTVaccination suppressesHelicobacter pyloricolonization but does not cure infection. Furthermore, postvaccination gastritis, likely induced by enhanced host response to residual colonization, may exacerbate disease. The goal of this study was to determine if adoptive transfer of C57BL/6 splenocytes to C57BL/6scid/scid(severe combined immunodeficient [SCID]) mice cures infection without exacerbating gastritis.H. pylori-infected and uninfected C57BL/6 mice and SCID recipients of normal splenocytes were killed at intervals between 5 and 51 weeks after infection. Colonization and gastritis were quantified, humoral immune responses were determined by enzyme-linked immunosorbent assay, and cellular immune responses were determined by delayed-type hypersensitivity response and by a proliferative response of cultured splenocytes toH. pylorisonicate. In infected C57BL/6 mice, gastritis developed gradually and bacterial colonization diminished but persisted throughout the experiment. In contrast, gastritis in infected recipient SCID mice developed rapidly and bacterial colonization decreased precipitously. Gastritis in those mice peaked 9 weeks after adoptive transfer, however, and began to resolve. By 45 weeks after transfer, gastritis had returned to background levels and bacteria were no longer detectable. Resolution of gastritis and elimination of infection were associated with a cellular but not humoral immune response toH. pyloriantigens. These results demonstrate that although the host response fails to clear bacterial colonization in normal mice, enhanced cellular immune responses in recipient SCID mice are capable of clearingH. pyloriinfection and allowing resolution of gastritis. Thus, immune mechanisms of cure exist, and effective and safe vaccination protocols may be feasible.
Macrophage-Derived Cell Lines Do Not Express Proinflammatory Cytokines after Exposure to
Bacillus anthracis
Lethal Toxin
Authors: Erwin James L. , DaSilva Luis M. , Bavari Sina , Little Stephen F. , Friedlander Arthur M. , Chanh Tran C. 
Published: July 2002

ABSTRACT

We present evidence that
Bacillus anthracis
lethal toxin (LT) suppresses rather than induces proinflammatory cytokine production in macrophages. Suppression is observed with extremely low levels of LT and involves inhibition of transcription of cytokine messenger RNA. Thus, LT may contribute to anthrax pathogenesis by suppressing the inflammatory response.