bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influenza Virus NS Vectors Expressing theMycobacterium tuberculosisESAT-6 Protein Induce CD4+Th1 Immune Response and Protect Animals against Tuberculosis Challenge
Authors: Sereinig Sabine , Stukova Marina , Zabolotnyh Natalia , Ferko Boris , Kittel Christian , Romanova Julia , Vinogradova Tatiana , Katinger Hermann , Kiselev Oleg , Egorov Andrej 
Published: August 2006

ABSTRACTInfection withMycobacterium tuberculosisremains a major cause of morbidity and mortality all over the world. Since the effectiveness of the only available tuberculosis vaccine,Mycobacterium bovisbacillus Calmette-Guérin (BCG), is suboptimal, there is a strong demand to develop new tuberculosis vaccines. As tuberculosis is an airborne disease, the intranasal route of vaccination might be preferable. Live influenza virus vaccines might be considered as potential vectors for mucosal immunization against various viral or bacterial pathogens, includingM. tuberculosis. We generated several subtypes of attenuated recombinant influenza A viruses expressing the 6-kDa early secretory antigenic target protein (ESAT-6) ofM. tuberculosisfrom the NS1 reading frame. We were able to demonstrate the potency of influenza virus NS vectors to induce anM. tuberculosis-specific Th1 immune response in mice. Moreover, intranasal immunization of mice and guinea pigs with such vectors induced protection against mycobacterial challenge, similar to that induced by BCG vaccination.
Early Appearance of Bactericidal Antibodies after Polysaccharide Challenge of Toddlers Primed with a Group C Meningococcal Conjugate Vaccine: What Is Its Role in the Maintenance of Protection?
Authors: Tsai Theodore F. , Borrow Ray , Gnehm Hanspeter E. , Vaudaux Bernard , Heininger Ulrich , Desgrandchamps Daniel , Aebi Christoph , Balmer Paul , Pedersen Ronald D. , Fritzell Bernard , Siegrist Claire-Anne 
Published: August 2006

ABSTRACT

The contribution of memory responses after meningococcal vaccination to protection may depend on the rapidity of the response. Toddlers were challenged with a licensed polysaccharide (PS) vaccine 1 year after vaccination with a single dose of meningococcal group C-CRM
197
conjugate (MCC) vaccine at the age of 12 to 15 months. Bactericidal antibodies and immunoglobulin G (IgG) antibodies detected by an enzyme-linked immunosorbent assay (ELISA) were measured before challenge and 4, 7, 14, or 21 Days later (“Days” refer to treatment groups, “days” to sampling days). Among 281 subjects in the intent-to-treat population, 173 per-protocol (PP) subjects were challenged with 10 μg PS antigen and 103 others with a 50-μg PS vaccinating dose. Capsular PS-specific ELISA IgG titers were negligible in baseline samples and increased only twofold within 4 days of PS administration. In contrast, the proportion of PP subjects with serum bactericidal antibody (SBA) titers of ≥1:8 or ≥1:128 increased, respectively, from 41% and 16% before challenge to 84% and 74% at Day 4 and to 100% and 97% at Day 7. Recipients of 50 μg PS responded with similar kinetics but showed a trend toward higher antibody levels. Unexpectedly, 69% of subjects bled on days 2 to 3 already had achieved SBA titers of ≥1:8. The majority of toddlers previously immunized with MCC and challenged 1 year later with PS antigen mounted protective levels of bactericidal antibody within 2 to 4 days.
Plant-Produced Cottontail Rabbit Papillomavirus L1 Protein Protects against Tumor Challenge: a Proof-of-Concept Study
Authors: Kohl T. , Hitzeroth I. I. , Stewart D. , Varsani A. , Govan V. A. , Christensen N. D. , Williamson A.-L. , Rybicki E. P. 
Published: August 2006

ABSTRACTThe native cottontail rabbit papillomavirus (CRPV) L1 capsid protein gene was expressed transgenically viaAgrobacterium tumefacienstransformation and transiently via a tobacco mosaic virus (TMV) vector inNicotianaspp. L1 protein was detected in concentrated plant extracts at concentrations up to 1.0 mg/kg in transgenic plants and up to 0.4 mg/kg in TMV-infected plants. The protein did not detectably assemble into viruslike particles; however, immunoelectron microscopy showed presumptive pentamer aggregates, and extracted protein reacted with conformation-specific and neutralizing monoclonal antibodies. Rabbits were injected with concentrated protein extract with Freund's incomplete adjuvant. All sera reacted with baculovirus-produced CRPV L1; however, they did not detectably neutralize infectivity in an in vitro assay. Vaccinated rabbits were, however, protected against wart development on subsequent challenge with live virus. This is the first evidence that a plant-derived papillomavirus vaccine is protective in an animal model and is a proof of concept for human papillomavirus vaccines produced in plants.
Porcine Circovirus Type 2 Infection Decreases the Efficacy of a Modified Live Porcine Reproductive and Respiratory Syndrome Virus Vaccine
Authors: Opriessnig T. , McKeown N. E. , Harmon K. L. , Meng X. J. , Halbur P. G. 
Published: August 2006

ABSTRACTPorcine reproductive and respiratory syndrome virus (PRRSV)-induced pneumonia is a major problem, and vaccination is used to reduce losses associated with PRRSV. Porcine circovirus type 2 (PCV2) causes lymphoid depletion, and there is concern that this adversely affects the immune response. The objective of this study was to investigate the effect of PCV2 infection on the efficacy of modified live virus (MLV) PRRSV vaccine. Sixty-nine 2-week-old pigs were randomly assigned to one of seven groups of 9 to 10 pigs each. At 6 weeks of age, pigs in groups 4, 5, and 6 were inoculated intranasally with PCV2 ISU-40895. At 8 weeks of age, groups 3, 4, 6, and 7 were vaccinated with a PRRSV MLV vaccine. At 12 weeks of age, groups 2, 3, and 4 were challenged with PRRSV SDSU73. All pigs were necropsied 14 days after PRRSV challenge. PCV2-infected, PRRSV-vaccinated, and PRRSV-challenged pigs had significantly (P< 0.05) more-severe macroscopic lung lesions than did the PRRSV-vaccinated and PRRSV-challenged pigs that were not exposed to PCV2 prior to PRRSV vaccination. Nonvaccinated PRRSV-infected pigs had a significantly (P< 0.001) higher incidence of PRRSV antigen in lungs than did all other groups except the group infected with PCV2 prior to PRRSV vaccination and challenge. The nonvaccinated PRRSV-challenged group and the group challenged with PCV2 prior to PRRSV vaccination and challenge had significantly (P< 0.001) lower average daily weight gain than did the control and the vaccinated groups. This work suggests that PCV2 infection has an adverse effect on the development of protective immunity induced by PRRSV vaccine.
Regulation of Lipopolysaccharide-Induced Interleukin-12 Production by Activation of Repressor Element GA-12 through Hyperactivation of the ERK Pathway
Authors: Saito Shinji , Matsuura Motohiro , Hirai Yoshikazu 
Published: August 2006

ABSTRACTInterleukin-12 (IL-12) functions as a representative lipopolysaccharide (LPS) mediator in both innate and adaptive immunity. We investigated the regulation of LPS-induced IL-12 production by mouse macrophages. In response to LPS, peritoneal macrophages produced bioactive IL-12 p70, a heterodimer (p40/p35) of subunits, but macrophage lines such as J774.1 and RAW264.7 did not. Induction of the p35 subunit was impaired in both cell lines, and additional impairment of p40 induction was observed in RAW264.7 cells. These results suggest that some negative regulatory mechanisms against LPS-induced IL-12 p40 production are constitutively functioning in RAW264.7 cells but not in the other types of cells. Activation of GA-12 (a repressor element of IL-12 p40), rather than suppression of promoter elements, such as binding sites for NF-κB, AP-1, and IRF-1, was detected in LPS-stimulated RAW264.7 cells, accompanying hyperactivation of extracellular signal-related kinase (ERK). When ERK activation was suppressed by an inhibitor (U0126), production of p40 rose from an undetectable to a substantial level and GA-12 activation decreased. In peritoneal macrophages, stimulation with a high dose of LPS reduced p40 production with enhanced activation of ERK. Pretreatment of the cells with phorbol myristate acetate to enhance ERK activation reduced p40 production in response to the optimal LPS stimulation. Taken together, these results demonstrate that hyperactivation of the ERK pathway plays a role in upstream signaling for the activation of GA-12, leading to the repression of IL-12 p40 production in mouse macrophages.
Association of CD14 Promoter Polymorphism with Otitis Media and Pneumococcal Vaccine Responses
Authors: Wiertsema S. P. , Khoo S.-K. , Baynam G. , Veenhoven R. H. , Laing I. A. , Zielhuis G. A. , Rijkers G. T. , Goldblatt J. , LeSouëf P. N. , Sanders E. A. M. 
Published: August 2006

ABSTRACTInnate immunity is of particular importance for protection against infection during early life, when adaptive immune responses are immature. CD14 plays key roles in innate immunity, including in defense against pathogens associated with otitis media, a major pediatric health care issue. The T allele of the CD14 C-159T polymorphism has been associated with increased serum CD14 levels. Our objective was to investigate the hypothesis that the CD14 C-159T allele is protective against recurrent acute otitis media in children. The association between the CD14 promoter genotype and the number of acute otitis media episodes was evaluated both retrospectively and prospectively in a cohort of 300 children. Serotype-specific immunoglobulin G (IgG) antibody responses after pneumococcal vaccinations were examined according to CD14 genotype to compare immune responsiveness across genotypes. An age-dependent association was found: compared with that for CC homozygotes aged between 12 to 24 months, TT homozygotes had fewer episodes of acute otitis media (79 versus 41%, respectively;P= 0.004); this relationship was absent in older children. Additionally, TT homozygotes showed higher serotype-specific anti-pneumococcal IgG antibody levels. Our data suggest that genetic variation in CD14, a molecule at the interface of innate and adaptive immune responses, plays a key role in the defense against middle ear disease in childhood and in pneumococcal vaccine responsiveness. These findings are likely to be important to these and other immune-mediated outcomes in early life.
A Novel Double-Antigen Sandwich Enzyme-Linked Immunosorbent Assay for Measurement of Antibodies against Rabies Virus
Authors: Yang Li-Min , Zhao Liang-Zhen , Hu Rong-Liang , Shi Zhen-Sheng , Liu Wen-Jun 
Published: August 2006

ABSTRACT
A novel double-antigen sandwich enzyme-linked immunosorbent assay (ELISA) was developed to measure rabies antibodies in dogs. In contrast to the 4 days required for detecting rabies antibody with conventional rabies antibody virus neutralization assays, this ELISA can be completed in hours, without using live virus, in routine laboratories.
Mycobacterium tuberculosis
HBHA Protein Reacts Strongly with the Serum Immunoglobulin M of Tuberculosis Patients
Authors: Shin A-Rum , Lee Kil-Soo , Lee Ji-Sook , Kim Su-Young , Song Chang-Hwa , Jung Saet-Byel , Yang Chul-Su , Jo Eun-Kyeong , Park Jeong-Kyu , Paik Tae-Hyun , Kim Hwa-Jung 
Published: August 2006

ABSTRACT

Identification and characterization of serologically active mycobacterial antigens are prerequisites for the development of diagnostic reagents. We examined the humoral immune responses of active tuberculosis (TB) patients against Triton-soluble proteins extracted from
Mycobacterium tuberculosis
by immunoblotting. A 29-kDa protein reacted with immunoglobulin M (IgM) in the pooled sera of the patients, and its N-terminal amino acid sequence matched that of the heparin-binding hemagglutinin (HBHA). Recombinant full-length HBHA was expressed in
Escherichia coli
(rEC-HBHA) and
M. smegmatis
(rMS-HBHA). In immunoblot analysis, the IgM antibodies of the TB patients reacted strongly with rMS-HBHA but not with rEC-HBHA, whereas the IgG antibodies of these patients reacted weakly with both recombinant HBHA proteins. In enzyme-linked immunosorbent assay analysis using rMS-HBHA and 85B as antigens, the mean levels and sensitivities of the anti-HBHA IgM antibodies of the TB patients were significantly higher than those of the anti-antigen 85B IgM antibodies, while the IgG antibodies showed the opposite results. Of interest in this respect, the pooled sera from the TB patients that contained anti-HBHA IgM antibodies neutralized the entry of
M. tuberculosis
into epithelial cells. These findings suggest that IgM antibody to HBHA may play a role in protection against extrapulmonary dissemination.
Group B Streptococcal Type II and III Conjugate Vaccines: Physicochemical Properties That Influence Immunogenicity
Authors: Michon Francis , Uitz Catherine , Sarkar Arun , D'Ambra Anello J. , Laude-Sharp Maryline , Moore Samuel , Fusco Peter C. 
Published: August 2006

ABSTRACTRecent efforts toward developing vaccines against group B streptococci (GBS) have focused on increasing the immunogenicity of GBS polysaccharides by conjugation to carrier proteins. However, partial depolymerization of GBS polysaccharides for the production of vaccines is a difficult task because of their acid-labile, antigenically critical sialic acids. Here we report a method for the partial depolymerization of type II and III polysaccharides by mild deaminative cleavage to antigenic fragments with reducing-terminal 2,5-anhydro-d-mannose residues. Through the free aldehydes of their newly formed end groups, the fragments were conjugated to tetanus toxoid by reductive amination. The resulting conjugates stimulated the production in animals of high-titer type II- and III-specific antibodies which induced opsonophagocytic killing of type II and III strains of group B streptococci. For the type II conjugates, immunogenicity increased as oligosaccharide size decreased, whereas for type III conjugates, the size of the oligosaccharides did not significantly influence immunogenicity. When oligosaccharides of defined size were conjugated through sialic acid residues, the resulting cross-linkages were shown to affect immunogenicity. When oligosaccharides were conjugated through terminal aldehyde groups generated by deamination, modification of the exocyclic chain of sialic acid did not influence immunogenicity.
Cloning, Characterization, and Expression ofBartonella henselae p26
Authors: Werner Jonathan A. , Feng Sunlian , Kasten Rickie W. , Hodzic Emir , Chomel Bruno B. , Barthold Stephen W. 
Published: August 2006

ABSTRACTIn order to identify immunoreactiveBartonella henselaeproteins,B. henselaeantiserum from an experimentally infected cat was used to screen aB. henselaegenomic DNA expression library. One immunoreactive phage clone contained a gene (p26) with significant nucleotide identity with orthologs in brucellae, bartonellae, and several plant-associated bacteria.p26gene sequences from fourB. henselaestrains, oneB. koehleraestrain, and oneB. clarridgeiaestrain were cloned. Comparative nucleotide sequence analysis showed thatp26is a potential marker for molecular diagnosis of infection, as well as for identification to species level and genotyping ofBartonellasp. isolates. Alignment of the predicted amino acid sequences illustrated conserved putative protein features including a hydrophobic transmembrane region, a peptide cleavage site, and four dominant antigenic sites. Expression ofp26inEscherichia coliproduced two proteins (26 and 27.5 kDa), both of which were reactive with feline anti-B. henselaeantisera. Furthermore, murine hyperimmune serum raised against either recombinant protein reacted with both proteins. No reactivity to either recombinant protein was detected in nonimmune serum, and reactivity persisted as long as 20 weeks for one cat. Thep26protein product is an immunodominant antigen that is expressed during infection in cats as a preprotein and is subsequently cleaved to form mature P26.
Anti-CD25 Antibody Treatment of Mice Vaccinated and Challenged withBorreliaspp. Does Not Exacerbate Arthritis but Inhibits Borreliacidal Antibody Production
Authors: Nardelli Dean T. , Warner Thomas F. , Callister Steven M. , Schell Ronald F. 
Published: August 2006

ABSTRACTCD4+CD25+T cells are a population of regulatory T cells responsible for the modulation of the immune response in several autoimmune and infectious disease models. We previously showed that adoptive transfer of enriched CD4+CD25+T cells also plays a major role in the prevention of arthritis inBorrelia-vaccinated (Borrelia burgdorferiisolate 297) and -challenged (B. bissettii) mice. Here, we present evidence that administration of anti-CD25 antibody at the time of challenge or at later intervals fails to enhance the development of severe destructive osteoarthropathy inBorrelia-vaccinated C57BL mice. However,Borrelia-vaccinated and -challenged mice receiving anti-CD25 antibody developed decreased borreliacidal antibody titers compared to vaccinated and challenged controls. These findings suggest that additional mechanisms besides CD4+CD25+T cells are involved in the regulation of the immune response toBorreliainfection following vaccination.
A Highly Sensitive and Subspecies-Specific Surface Antigen Enzyme- Linked Immunosorbent Assay for Diagnosis of Johne's Disease
Authors: Eda Shigetoshi , Bannantine John P. , Waters W. R. , Mori Yasuyuki , Whitlock Robert H. , Scott M. Cathy , Speer C. A. 
Published: August 2006

ABSTRACT

Johne's disease (JD), or paratuberculosis, caused by
Mycobacterium avium
subsp.
paratuberculosis
, is one of the most widespread and economically important diseases of livestock and wild ruminants worldwide. Control of JD could be accomplished by diagnosis and good animal husbandry, but this is currently not feasible because commercially available diagnostic tests have low sensitivity levels and are incapable of diagnosing prepatent infections. In this study, a highly sensitive and subspecies-specific enzyme-linked immunosorbent assay was developed for the diagnosis of JD by using antigens extracted from the surface of
M. avium
subsp.
paratuberculosis
. Nine different chemicals and various intervals of agitation by vortex were evaluated for their ability to extract the surface antigens. Various quantities of surface antigens per well in a 96-well microtiter plate were also tested. The greatest differences in distinguishing between JD-positive and JD-negative serum samples by ethanol vortex enzyme-linked immunosorbent assay (EVELISA) were obtained with surface antigens dislodged from 50 μg/well of bacilli treated with 80% ethanol followed by a 30-second interval of agitation by vortex. The diagnostic specificity and sensitivity of the EVELISA were 97.4% and 100%, respectively. EVELISA plates that had been vacuum-sealed and then tested 7 weeks later (the longest interval tested) had diagnostic specificity and sensitivity rates of 96.9 and 100%, respectively. In a comparative study involving serum samples from 64 fecal culture-positive cattle, the EVELISA identified 96.6% of the low-level fecal shedders and 100% of the midlevel and high-level shedders, whereas the Biocor ELISA detected 13.7% of the low-level shedders, 25% of the mid-level shedders, and 96.2% of the high-level shedders. Thus, the EVELISA was substantially superior to the Biocor ELISA, especially in detecting low-level and midlevel shedders. The EVELISA may form the basis for a highly sensitive and subspecies-specific test for the diagnosis of JD.
Use of Immunoglobulin G Avidity To Determine the Course of Disease in Visceral and Post-Kala-Azar Dermal Leishmaniasis Patients
Authors: Singh Redhu Naresh , Dey Ayan , Balooni Veena , Singh Sarman 
Published: August 2006

ABSTRACT

In the present study, anti-
Leishmania
immunoglobulin G (IgG) avidity was used to estimate the approximate time of disease manifestation. Significant differences (
P
< 0.0001) were found between the levels of anti-rKE-16 IgG avidity in leishmaniasis patients with recent and chronic diseases. More than 76% of patients with an illness duration of less than 6 months had avidity of less than 70%, 94% of patients had less than 80% avidity, and all (100%) patients with illness of more than 6 months had avidity values higher than 70%. The study showed that avidity could successfully be used to pinpoint the duration of leishmaniasis.
DNA Vaccine UsingMycobacterium bovisAg85B Antigen Induces Partial Protection against Experimental Infection in BALB/c Mice
Authors: Teixeira Francisco M. , Teixeira Henrique C. , Ferreira Ana Paula , Rodrigues Michele F. , Azevedo Vasco , Macedo Gilson C. , Oliveira Sergio C. 
Published: August 2006

ABSTRACTBovine tuberculosis is a major cause of economic loss in countries where it is endemic, and in some countries, it may be a significant zoonotic disease problem. Therefore, new strategies for vaccine development are required, and among them, genetic immunization has potential value. The main goal of this study was to test theMycobacterium bovisAg85B gene as a DNA vaccine following challenge with anM. bovisvirulent strain (ATCC 19274). Groups of BALB/c mice (n= 10) were immunized four times intramuscularly with the pCI-Ag85B construct or the pCI vector alone as the control. High titers of total immunoglobulin G (IgG), IgG1, and IgG2a anti-Ag85B were measured in pCI-Ag85B immunized mice when compared to the pCI control group. Regarding cellular immunity, significant levels of gamma interferon (IFN-γ) (1,100 ± 157 pg/ml) and tumor necrosis factor alpha (650 ± 42 pg/ml) but not interleukin-4 were detected in splenocyte culture supernatants of pCI-Ag85B-vaccinated mice following stimulation with recombinant Ag85B. Further, the main source of IFN-γ is CD8+T cells, as demonstrated by intracellular cytokine staining. As far as protection, a significant reduction in bacterial load in spleens (P< 0.05) was detected in pCI-Ag85B-immunized mice compared to the pCI vector control group. The results obtained here suggest that use of the Ag85B DNA vaccine is a promising strategy to controlM. bovisinfection due to its ability to induce a Th1 type of immune response. However, protective efficacy needs to be improved, since partial protection was achieved in spleens but not in lungs of vaccinated mice.
Reduced Expression of Toll-Like Receptor 2 on Peripheral Monocytes in Patients with Chronic Hepatitis B
Authors: Riordan Stephen M. , Skinner Narelle , Kurtovic Jelica , Locarnini Stephen , Visvanathan Kumar 
Published: August 2006

ABSTRACT
Persistent infection with hepatitis B virus (HBV) likely depends on viral inhibition of host defenses. We report that chronic hepatitis B e antigen-positive HBV infection is associated with a significant reduction in peripheral blood monocyte expression of Toll-like receptor 2, a key component of innate immunity, thereby providing a mechanism by which wild-type HBV may establish persistent infection.
THE TSP AND THE SUM OF ITS MARGINAL VALUES
Authors: DROR MOSHE , LEE YUSIN , ORLIN JAMES B. , POLISHCHUK VALENTIN 
Published: August 2006

This paper introduces a new notion related to the traveling salesperson problem (TSP) — the notion of the TSP ratio. The TSP ratio of a TSP instance I is the sum of the marginal values of the nodes of I divided by the length of the optimal TSP tour on I, where the marginal value of a node i ∈ I is the difference between the length of the optimal tour on I and the length of the optimal tour on I\i. We consider the problem of establishing exact upper and lower bounds on the TSP ratio. To our knowledge, this problem has not been studied previously. We present a number of cases for which the ratio is never greater than 1. We establish a tight upper bound of 2 on the TSP ratio of any metric TSP. For the TSP on six nodes, we determine the maximum ratio of 1.5 in general, 1.2 for the case of metric TSP, and 10/9 for the geometric TSP in the L1 metric. We also compute the TSP ratio experimentally for a large number of random TSP instances on small number of points.