bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nasal and Vaginal Vaccinations Have Differential Effects on Antibody Responses in Vaginal and Cervical Secretions in Humans
Authors: Johansson Eva-Liz , Wassén Lotta , Holmgren Jan , Jertborn Marianne , Rudin Anna 
Published: July 2002

ABSTRACTSexually transmitted diseases are a major health problem worldwide, but there is still a lack of knowledge about how to induce an optimal immune response in the genital tract of humans. In this study we vaccinated 21 volunteers nasally or vaginally with the model mucosal antigen cholera toxin B subunit and determined the level of specific immunoglobulin A (IgA) and IgG antibodies in vaginal and cervical secretions as well as in serum. To assess the hormonal influence on the induction of antibody responses after vaginal vaccination, we administered the vaccine either independently of the stage in the menstrual cycle or on days 10 and 24 in the cycle in different groups of subjects. Vaginal and nasal vaccinations both resulted in significant IgA and IgG anti-cholera toxin B subunit responses in serum in the majority of the volunteers in the various vaccination groups. Only vaginal vaccination given on days 10 and 24 in the cycle induced strong specific antibody responses in the cervix with 58-fold IgA and 16-fold IgG increases. In contrast, modest responses were seen after nasal vaccination and in the other vaginally vaccinated group. Nasal vaccination was superior in inducing a specific IgA response in vaginal secretions, giving a 35-fold increase, while vaginal vaccination induced only a 5-fold IgA increase. We conclude that a combination of nasal and vaginal vaccination might be the best vaccination strategy for inducing protective antibody responses in both cervical and vaginal secretions, provided that the vaginal vaccination is given on optimal time points in the cycle.
Gravidity-Dependent Production of Antibodies That Inhibit Binding ofPlasmodium falciparum-Infected Erythrocytes to Placental Chondroitin Sulfate Proteoglycan during Pregnancy
Authors: O'Neil-Dunne Iona , Achur Rajeshwara N. , Agbor-Enoh Sean T. , Valiyaveettil Manojkumar , Naik Ramachandra S. , Ockenhouse Christian F. , Zhou Ainong , Megnekou Rosette , Leke Rose , Taylor Diane W. , Gowda D. Channe 
Published: July 2002

ABSTRACTDuring pregnancy,Plasmodium falciparum-infected erythrocytes sequester in the placenta by adhering to chondroitin 4-sulfate, creating a risk factor for both the mother and the fetus. The primigravidae are at higher risk for placental malaria than the multigravidae. This difference in susceptibility has been attributed to the lack of antibodies that block the adhesion of infected erythrocytes to placental chondroitin 4-sulfate in primigravid women. However, recent results show that many primigravidae at term have antibody levels similar to those of multigravidae, and thus the significance of antiadhesion antibodies in providing protection against malaria during pregnancy remains unclear. In this study, we analyzed plasma samples from women of various gravidities at different gestational stages for antiadhesion antibodies. The majority of women, regardless of gravidity, had similar levels of antibodies at term. Most primigravidae had low levels of or no antiadhesion antibodies prior to ∼20 weeks of pregnancy and then produced antibodies. Multigravidae also lacked antibodies until ∼12 weeks of pregnancy, but thereafter they efficiently produced antibodies. In pregnant women who had placental infection at term, higher levels of antiadhesion antibodies correlated with lower levels of placental parasitemia. The difference in kinetics of antibody production between primigravidae and multigravidae correlated with the prevalence of malaria in these groups, suggesting that antibodies are produced during pregnancy in response to placental infection. The early onset of efficient antibody response in multigravidae and the delayed production to antibodies in primigravidae appear to account for the gravidity-dependent differential susceptibilities of pregnant women to placental malaria.
Protective KilledLeptospira borgpeterseniiVaccine Induces Potent Th1 Immunity Comprising Responses by CD4 and γδ T Lymphocytes
Authors: Naiman Brian M. , Alt David , Bolin Carole A. , Zuerner Richard , Baldwin Cynthia L. 
Published: July 2002

ABSTRACTLeptospira borgpeterseniiserovar hardjo is the most common cause of bovine leptospirosis and also causes zoonotic infections of humans. A protective killed vaccine against serovar hardjo was shown to induce strong antigen-specific proliferative responses by peripheral blood mononuclear cells (PBMC) from vaccinated cattle by 2 months after the first dose of vaccine. This response was absent from nonvaccinated control cattle. The mean response peaked by 2 months after completion of the two-dose vaccination regimen, and substantial proliferation was measured in in vitro cultures throughout the 7 months of the study period. Variations in magnitude of the response occurred among the vaccinated animals, but by 7 months postvaccination there was a substantial antigen-specific response with PBMC from all vaccinated animals. Up to one-third of the PBMC from vaccinated animals produced gamma interferon (IFN-γ) after 7 days in culture with antigen, as ascertained by flow cytometric analysis, and significant levels of IFN-γ were measured in culture supernatants by enzyme-linked immunosorbent assay. Two-color immunofluorescence revealed that one-third of the IFN-γ-producing cells were γδ T cells, with the remaining cells being CD4+T cells. The significance of this study is the very potent Th1-type immune response induced and sustained following vaccination with a killed bacterial vaccine adjuvanted with aluminum hydroxide and the involvement of γδ T cells in the response. Moreover, induction of this Th1-type cellular immune response is associated with the protection afforded by the bovine leptospiral vaccine againstL. borgpeterseniiserovar hardjo.
Protective Effect ofLactobacillus caseiStrain Shirota on Shiga Toxin-ProducingEscherichia coliO157:H7 Infection in Infant Rabbits
Authors: Ogawa Michinaga , Shimizu Kensuke , Nomoto Koji , Takahashi Masatoshi , Watanuki Masaaki , Tanaka Ryuichiro , Tanaka Tetsuya , Hamabata Takashi , Yamasaki Shinji , Takeda Yoshifumi 
Published: July 2002

ABSTRACTWe examined colonization patterns of Shiga toxin-producingEscherichia coli(STEC), concentrations of Shiga toxins (Stxs) and specific immunoglobulin A (lgA) against Stxs and STEC bacterial cell surface antigen in various portions of the gastrointestinal tract in an infant rabbit infection model. After inoculation of 3-day-old infant rabbits with STEC strain 89020087 at low doses (∼103CFU/body), numbers of colonizing STEC bacteria and concentrations of Stxs in the intestine increased dramatically and the animals developed diarrhea within a couple of days after infection. Daily administration ofLactobacillus caseifrom the day of birth dramatically decreased the severity of diarrhea and lowered STEC colonization levels in the gastrointestinal tract 100-fold day 7 after infection. Both Stx1 and Stx2 concentrations in the intestines and histological damage to the intestinal mucus induced by STEC infection were decreased by the administration ofL. casei. Examination of the concentrations of volatile fatty acids and pH of the intestinal contents revealed that the protective effect ofL. caseiadministration against STEC infection was not due to fermented products such as lactic acid in the gastrointestinal tract. Administration ofL. caseiincreased levels of lgAs against Stx1, Stx2, and formalin-killed STEC cells in the colon approximately two-, four-, and threefold, respectively, compared with those of the untreated controls by day 7 after infection. These results suggest that administration ofL. caseistrain Shirota enhances the local immune responses to STEC cells and Stxs and leads to elimination of STEC and thus decreases Stx concentrations in the intestines.
Synthetic 6B Di-, Tri-, and Tetrasaccharide-Protein Conjugates Contain Pneumococcal Type 6A and 6B Common and 6B- Specific Epitopes That Elicit Protective Antibodies in Mice
Authors: Jansen Wouter T. M. , Hogenboom Sietske , Thijssen Mark J. L. , Kamerling Johannis P. , Vliegenthart Johannes F. G. , Verhoef Jan , Snippe Harm , Verheul André F. M. 
Published: July 2002

ABSTRACT

The immunogenicity and protective capacity of
Streptococcus pneumoniae
6B capsular polysaccharide (PS)-derived synthetic phosphate-containing disaccharide (Rha-ribitol-
P
-), trisaccharide (ribitol-
P
-Gal-Glc-), and tetrasaccharide (Rha-ribitol-
P
-Gal-Glc-)-protein conjugates in rabbits and mice were studied. In rabbits, all saccharides conjugated to keyhole limpet hemocyanin (KLH) evoked high levels of pneumococcal (Pn) type 6B antibodies that facilitated type-specific phagocytosis. Unlike the disaccharide rabbit antisera, tri- and tetrasaccharide rabbit antisera also reacted with 6A PS in an enzyme-linked immunosorbent assay (ELISA) and promoted phagocytosis of 6A pneumococci. All these rabbit antisera passively protected mice against a Pn 6B challenge. The disaccharide conjugate-induced antiserum, however, failed to protect mice against a 6A challenge. In mice, phagocytic and protective anti-Pn 6B antibodies were only induced by the tetrasaccharide conjugate and not by PS 6B or PS 6B-protein conjugates. These antibodies did not cross-react with 6A PS in ELISA and were unable to phagocytize 6A pneumococci. In conclusion, the disaccharide and tetrasaccharide conjugates already contain epitopes capable of inducing 6B-specific, fully protective antibodies in rabbits and mice, respectively.
Efficacy of Two Alternate Vaccines Based onPlasmodium falciparumMerozoite Surface Protein 1 in anAotusChallenge Trial
Authors: Stowers Anthony W. , Cioce Vittoria , Shimp Richard L. , Lawson Mark , Hui George , Muratova Olga , Kaslow David C. , Robinson Robin , Long Carole A. , Miller Louis H. 
Published: July 2002

ABSTRACTIn an attempt to produce a more defined, clinical-grade version of a vaccine based onPlasmodium falciparummerozoite surface protein 1 (MSP1), we evaluated the efficacy of two recombinant forms of MSP1 in anAotus nancymaichallenge model system. One recombinant vaccine, bvMSP142, based on the 42-kDa C-terminal portion of MSP1, was expressed as a secreted protein in baculovirus-infected insect cells. A highly pure baculovirus product could be reproducibly expressed and purified at yields in excess of 8 mg of pure protein per liter of culture. This protein, when tested for efficacy in theAotuschallenge model, gave significant protection, with only one of seven monkeys requiring treatment for uncontrolled parasitemia after challenge withP. falciparum. The second recombinant protein, P30P2MSP119, has been used in previous studies and is based on the smaller, C-terminal 19-kDa portion of MSP1 expressed inSaccharomyces cerevisiae. Substantial changes were made in its production process to optimize expression. The optimum form of this vaccine antigen (as judged by in vitro and in vivo indicators) was then evaluated, along with bvMSP142, for efficacy in theA. nancymaisystem. The new formulation of P30P3MSP119performed significantly worse than bvMSP142and appeared to be less efficacious than we have found in the past, with four of seven monkeys in the vaccinated group requiring treatment for uncontrolled parasitemia. With both antigens, protection was seen only when high antibody levels were obtained by formulation of the vaccines in Freund's adjuvant. Vaccine formulation in an alternate adjuvant, MF59, resulted in significantly lower antibody titers and no protection.
Analysis of Transcriptionally Active Gene Clusters of Major Outer Membrane Protein Multigene Family inEhrlichia canisandE. chaffeensis
Authors: Ohashi Norio , Rikihisa Yasuko , Unver Ahmet 
Published: July 2002

ABSTRACTEhrlichia canisandE. chaffeensisare tick-borne obligatory intramonocytic ehrlichiae that cause febrile systemic illness in humans and dogs, respectively. The current study analyzed the pleomorphic multigene family encoding approximately 30-kDa major outer membrane proteins (OMPs) ofE. canisandE. chaffeensis. Upstream fromsecAand downstream of hypothetical transcriptional regulator, 22 paralogs of theompgene family were found to be tandemly arranged except for one or two genes with opposite orientations in a 28- and a 27-kb locus in theE. canisandE. chaffeensisgenomes, respectively. Each locus consisted of three highly repetitive regions with four nonrepetitive intervening regions.E. canis, in addition, had a 6.9-kb locus which contained a repeat of three tandem paralogs in the 28-kb locus. These total 47 paralogous and orthologous genes encoded OMPs of approximately 30 to 35 kDa consisting of several hypervariable regions alternating with conserved regions. In the 5′-end half of the 27-kb locus or the 28-kb locus of eachEhrlichiaspecies, 14 paralogs were linked by short intergenic spaces ranging from −8 bp (overlapped) to 27 bp, and 8 remaining paralogs in the 3′-end half were connected by longer intergenic spaces ranging from 213 to 632 bp. All 22 paralogs, five unknown genes, andsecAin theompcluster inE. caniswere transcriptionally active in the monocyte culture, and the paralogs with short intergenic spaces were cotranscribed with their adjacent genes, including the respective intergenic spaces at both the 5′ and the 3′ sides. Althoughompgenes are diverse, our results suggest that the gene organization of the clusters and the gene locus are conserved between two species ofEhrlichiato maintain a unique transcriptional mechanism for adaptation to environmental changes common to them.
Different Subsets of Enteric Bacteria Induce and Perpetuate Experimental Colitis in Rats and Mice
Authors: Rath Heiko C. , Schultz Michael , Freitag René , Dieleman Levinus A. , Li Fengling , Linde Hans-Jörg , Schölmerich Jürgen , Sartor R. Balfour 
Published: July 2002

ABSTRACTResident bacteria are incriminated in the pathogenesis of experimental colitis and inflammatory bowel diseases. We investigated the relative roles of various enteric bacteria populations in the induction and perpetuation of experimental colitis. HLA-B27 transgenic rats received antibiotics (ciprofloxacin, metronidazole, or vancomycin-imipenem) in drinking water or water alone in either prevention or treatment protocols. Mice were treated similarly with metronidazole or vancomycin-imipenem before or after receiving 5% dextran sodium sulfate (DSS). Germfree transgenic rats were colonized with specific-pathogen-free enteric bacteria grown overnight either in anaerobic or aerobic atmospheres. Nontransgenic rats colonized with anaerobic bacteria served as negative controls. Although preventive metronidazole significantly attenuated colitis in transgenic rats and DSS-treated mice, it had no therapeutic benefit once colitis was established. Ciprofloxacin also partially prevented but did not treat colitis in B27 transgenic rats. In both animal models vancomycin-imipenem most effectively prevented and treated colitis. Germfree transgenic rats reconstituted with enteric bacteria grown under anaerobic conditions had more aggressive colitis than those associated with aerobic bacteria. These results suggest that a subset of resident luminal bacteria induces colitis, but that a complex interaction of commensal aerobic and anaerobic bacteria provides the constant antigenic drive for chronic immune-mediated colonic inflammation.
Profiles of Immunoglobulin M (IgM) and IgG Antibodies against Defined Carbohydrate Epitopes in Sera ofSchistosoma-Infected Individuals Determined by Surface Plasmon Resonance
Authors: van Remoortere Alexandra , van Dam Govert J. , Hokke Cornelis H. , van den Eijnden Dirk H. , van Die Irma , Deelder AndréM. 
Published: July 2002

ABSTRACTWe report here that sera of children and adults infected withSchistosoma mansoni, S. haematobium, orS. japonicumcontain antibodies against GalNAcβ1-4(Fucα1-2Fucα1-3)GlcNAc (LDN-DF) and to a lesser extent to Galβ1-4(Fucα1-3)GlcNAc (Lewisx) and GalNAcβ1-4GlcNAc (LDN). Surface plasmon resonance (SPR) spectroscopy was used to monitor the presence of serum antibodies to neoglycoconjugates containing these carbohydrate epitopes and to define the immunoglobulin M (IgM) and IgG subclass distribution of the antibodies. The serum levels of antibodies to LDN-DF are high related to LDN and Lewisxfor all examined groups ofSchistosoma-infected individuals. A higher antibody response to the LDN-DF epitope was found in sera of infected children than in sera of infected adults regardless of the schistosome species. With respect to the subclasses, we found surprisingly that individuals infected withS. japonicumhave predominantly IgG antibodies, while individuals infected withS. mansonimainly show an IgM response; high levels of both isotypes were measured in sera of individuals infected withS. haematobium. These data provide new insights in the human humoral immune response to schistosome-derived glycans.
Antibody Recognition of Rodent Malaria Parasite Antigens Exposed at the Infected Erythrocyte Surface: Specificity of Immunity Generated in Hyperimmune Mice
Authors: Mota Maria M. , Brown K. Neil , Do Rosário Virgilio E. , Holder Anthony A. , Jarra William 
Published: July 2002

ABSTRACTIn regions where malaria is endemic, inhabitants remain susceptible to repeated reinfection as they develop and maintain clinical immunity. This immunity includes responses to surface-exposed antigens onPlasmodiumsp.-infected erythrocytes. Some of these parasite-encoded antigens may be diverse and phenotypically variable, and the ability to respond to this diversity and variability is an important component of acquired immunity. Characterizing the relative specificities of antibody responses during the acquisition of immunity and in hyperimmune individuals is thus an important adjunct to vaccine research. This is logistically difficult to do in the field but is relatively easily carried out in animal models. Infections in inbred mice with rodent malaria parasitePlasmodium chabaudi chabaudiAS represent a good model forPlasmodium falciparumin humans. This model has been used in the present study in a comparative analysis of cross-reactive and specific immune responses in rodent malaria. CBA/Ca mice were rendered hyperimmune toP. chabaudi chabaudi(AS or CB lines) orPlasmodium berghei(KSP-11 line) by repeated infection with homologous parasites. Serum fromP. chabaudi chabaudiAS hyperimmune mice reacted with antigens released from disruptedP. chabaudi chabaudiAS-infected erythrocytes, butP. chabaudi chabaudiCB andP. bergheiKSP-11 hyperimmune serum also contained cross-reactive antibodies to these antigens. However, antibody activity directed against antigens exposed at the surfaces of intactP. chabaudi chabaudi-infected erythrocytes was mainly parasite species specific and, to a lesser extent, parasite line specific. Importantly, this response included opsonizing antibodies, which bound to infected erythrocytes, leading to their phagocytosis and destruction by macrophages. The results are discussed in the context of the role that antibodies to both variable and invariant antigens may play in protective immunity in the face of continuous susceptibility to reinfection.
Protective Role of Lung Surfactant Protein D in a Murine Model of Invasive Pulmonary Aspergillosis
Authors: Madan Taruna , Kishore Uday , Singh Mamta , Strong Peter , Hussain Ejaj M. , Reid Kenneth B. M. , Sarma P. Usha 
Published: July 2002

ABSTRACT

The protective effects of intranasal administration of amphotericin B (AmB), human SP-A, SP-D and a 60-kDa fragment of SP-D (rSP-D) were examined in a murine model of invasive pulmonary aspergillosis (IPA). The untreated group of IPA mice showed no survival at 7 days postinfection. Treatment with AmB, SP-D, and rSP-D increased the survival rate to 80, 60, and 80%, respectively, suggesting that SP-D (and rSP-D) can protect immunosuppressed mice from an otherwise fatal challenge with
Aspergillus fumigatus
conidia.
Interleukin-10 Regulates the Tissue Factor Activity of Monocytes in an In Vitro Model of Bacterial Endocarditis
Authors: Veltrop Marcel H. A. M. , Langermans Jan A. M. , Thompson Jan , Bancsi Maurice J. L. M. F. 
Published: July 2002

ABSTRACTMonocytes are important effector cells in the pathogenesis of bacterial endocarditis since they provide the tissue factor that activates the coagulation system and maintains established vegetations. Monocytes secrete cytokines that can modulate monocyte tissue factor activity (TFA), thereby affecting the formation and maintenance of vegetations. In this study, we show that monocytes cultured for 4 h on aStreptococcus sanguis-infected fibrin matrix mimicking the in vivo vegetational surface express high levels of TFA. This was accompanied by secretion of the proinflammatory cytokines tumor necrosis factor alpha (TNF-α), interleukin-1α (IL-1α), and IL-1β. After a 24-h incubation period the anti-inflammatory cytokine IL-10 could also be detected. Our data show that, whereas TNF-α and IL-1 have a minor role in the induction of TFA by monocytes cultured on a fibrin matrix, TNF-α but not IL-1 plays an important role in the induction of IL-10 by these cells. In turn, our data show that IL-10 is an important factor in the downregulation of monocyte TFA. In summary, we conclude that IL-10 is an important factor in the control of monocyte TFA in endocardial vegetations.
Vaccination against the Intracellular PathogensLeishmania majorandL. amazonensisby Directing CD40 Ligand to Macrophages
Authors: Chen Gang , Darrah Patricia A. , Mosser David M. 
Published: July 2002

ABSTRACTCD40 ligand (CD40L) is a potent inducer of interleukin-12 (IL-12) production from macrophages and dendritic cells. We show that combining CD40L with antigen derived fromLeishmaniais an effective way to preferentially induce type 1 immune responses to the antigen and to vaccinate mice against subsequent challenge with virulent organisms. Mice vaccinated in this way had smaller lesions, with more than 1,000-fold fewer parasites within them. To improve the efficiency of CD40L-induced immunopotentiation, we attempted to specifically direct CD40L to macrophages. We developed transfected cells expressing CD40L and a singleLeishmaniaantigen, gp63. These cells bound efficiently to macrophages and induced robust IL-12 production. Vaccination with these cotransfected cells provided a significant degree of protection against challenge with virulent organisms. CD40L was also adsorbed to the surface of virulentLeishmania. These organisms induced only modest lesions in genetically susceptible mice, and the lesions had an average of 105-fold fewer organisms within them relative to control mice. These studies suggest that CD40L could be exploited to improve vaccines against intracellular pathogens, especially those organisms that reside within cells expressing CD40 on their surface.