Clinical and Vaccine Immunology最新文献

{"title":"An Opsonic Phagocytosis Assay for Plasmodium falciparum Sporozoites","authors":"R. Steel, B. Sack, M. Tsuji, M. Navarro, Will Betz, Matthew E. Fishbaugher, E. Flannery, S. Kappe","doi":"10.1128/CVI.00445-16","DOIUrl":"https://doi.org/10.1128/CVI.00445-16","url":null,"abstract":"ABSTRACT Plasmodium falciparum malaria remains the deadliest parasitic disease worldwide. Vaccines targeting the preerythrocytic sporozoite and liver stages have the potential to entirely prevent blood-stage infection and disease, as well as onward transmission. Sporozoite surface and secreted proteins are leading candidates for inclusion in a preerythrocytic stage-specific, antibody-based vaccine. Preclinical functional assays to identify humoral correlates of protection in vitro and to validate novel sporozoite protein targets for inclusion in multisubunit vaccines currently do not consider the interaction of sporozoite-targeting antibodies with other components of the immune system. Here, we describe the development of a simple flow cytometric assay to quantitatively assess the ability of antibodies directed against P. falciparum sporozoites to facilitate their phagocytosis. We demonstrate that this sporozoite opsonic phagocytosis assay (SOPA) is compatible with both monoclonal antibodies and human immune serum and can be performed using cryopreserved P. falciparum sporozoites. This simple, accessible assay will aid with the assessment of antibody responses to vaccination with Plasmodium antigens and their interaction with phagocytic cells of the immune system.","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87819562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kinetics of Meningococcal Serogroup C-Specific Functional Antibody Levels Up to 15 Years after a Single Immunization with a Meningococcal Serogroup C Conjugate Vaccine during Adolescence","authors":"S. P. Stoof, M. V. van Ravenhorst, D. V. van Rooijen, Richarda M. de Voer, F. R. van der Klis, G. Boland, E. Sanders, G. Berbers, P. Teunis","doi":"10.1128/CVI.00429-16","DOIUrl":"https://doi.org/10.1128/CVI.00429-16","url":null,"abstract":"ABSTRACT Adolescent vaccination is now considered the key factor for offering direct protection against meningococcal disease but also for reducing carriage and transmission and, in this way, establishing herd protection. This study estimated age-dependent patterns in functional meningococcal serogroup C (MenC) antibody kinetics after primary MenC conjugate (MenCC) vaccination in adolescents. Serum samples (n = 1,676) were drawn from 2006 to 2011 from individuals aged 9 to 18 years at the time of primary MenCC vaccination in 2002. Functional antibody levels were measured with a serum bactericidal antibody assay (SBA) using rabbit complement. SBA titers gradually declined with time. Up to 9 years after primary vaccination, SBA titers were estimated to be higher in individuals who were aged 13 to 18 years at priming than in those who were aged 9 to 10 years at priming. Based on a linear mixed model, the higher functional antibody levels with age seem to be due to the achievement of higher peak levels upon vaccination rather than to lower rates of decline. It is estimated that 35 to 50% of individuals who received a single primary MenCC vaccination at an age of 9 to 18 years in 2002 will still have sufficient protective antibody levels 15 years later. Using a linear mixed model based on cohort data for a single dated serum sample per person, we were able to estimate the level of protection against MenC up to 15 years after a single vaccination. The current study shows that analysis of antibody kinetics can be done using cross-sectional serology data and is therefore relevant for future serosurveillance studies.","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"59 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88909178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trained Immunity and Susceptibility to HIV","authors":"S. Derrick","doi":"10.1128/CVI.00509-16","DOIUrl":"https://doi.org/10.1128/CVI.00509-16","url":null,"abstract":"ABSTRACT In this issue of Clinical and Vaccine Immunology, K. Jensen et al. (Clin Vaccine Immunol 24:e00360-16, 2017, https://doi.org/10.1128/CVI.00360-16 ) describe a dual-purpose attenuated Mycobacterium tuberculosis-simian immunodeficiency virus vaccine (AMTB-SIV). Interestingly, immunized infant macaques required fewer oral exposures to SIV to become infected relative to nonimmunized animals. The authors hypothesized that augmented susceptibility to SIV was due to activation of CD4+ T cells through trained immunity. This commentary explores the possible relationship between trained immunity, enhanced CD4 T cell responses, and increased susceptibility to human immunodeficiency virus (HIV).","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"69 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86154306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparisons of the Humoral and Cellular Immune Responses Induced by Live Attenuated Influenza Vaccine and Inactivated Influenza Vaccine in Adults","authors":"D. Hoft, Kathleen R. Lottenbach, Azra Blazevic, Aldin Turan, T. Blevins, Thomas Pacatte, Yinyi Yu, Michelle C. Mitchell, Stella G Hoft, R. Belshe","doi":"10.1128/CVI.00414-16","DOIUrl":"https://doi.org/10.1128/CVI.00414-16","url":null,"abstract":"ABSTRACT Both live attenuated influenza vaccines (LAIV) and inactivated influenza vaccines (IIV) induce protective immunity against influenza. There is evidence that LAIV induces superior protection in children, whereas IIV may induce superior protection in adults. The immune mechanisms responsible for these differences have not been identified. We previously compared LAIV and IIV in young children of 6 to 36 months of age, and we demonstrated that while both induced similar hemagglutination inhibition (HAI) antibody responses, only LAIV induced significant increases in T cell responses. In the present study, 37 healthy adult subjects of 18 to 49 years of age were randomized to receive seasonal influenza vaccination with LAIV or IIV. Influenza virus-specific HAI, T cell, and secretory IgA (sIgA) responses were studied pre- and postvaccination. In contrast to the responses seen in young children, LAIV induced only minimal increases in serum HAI responses in adults, which were significantly lower than the responses induced by IIV. Both LAIV and IIV similarly induced only transient T cell responses to replication-competent whole virus in adults. In contrast, influenza virus-specific sIgA responses were induced more strongly by LAIV than by IIV. Our previous studies suggest that LAIV may be more protective than IIV in young children not previously exposed to influenza virus or influenza vaccines due to increased vaccine-induced T cell and/or sIgA responses. Our current work suggests that in adults with extensive and partially cross-reactive preexisting influenza immunity, LAIV boosting of sIgA responses to hemagglutinin (HA) and non-HA antigenic targets expressed by circulating influenza virus strains may be an important additional mechanism of vaccine-induced immunity.","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75220726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small-Volume Adenosine, Lidocaine, and Mg2+ 4-Hour Infusion Leads to 88% Survival after 6 Days of Experimental Sepsis in the Rat without Antibiotics.","authors":"Maddison Jade Griffin,&nbsp;Hayley Louise Letson,&nbsp;Geoffrey Phillip Dobson","doi":"10.1128/CVI.00390-16","DOIUrl":"https://doi.org/10.1128/CVI.00390-16","url":null,"abstract":"<p><p>Innovative host-directed drug therapies are urgently required to treat sepsis. We tested the effect of a small-volume 0.9% NaCl adenosine, lidocaine, and Mg²⁺ (ALM) bolus and a 4-h intravenous infusion on survivability in the rat model of polymicrobial sepsis over 6 days. ALM treatment led to a significant increase in survivability (88%) compared to that of controls (25%). Four controls died on day 2 to 3, and two died on day 5. Early death was associated with elevated plasma and lung inflammatory markers (interleukin-6 [IL-6], IL-1β, C-reactive protein), reduced white blood cell (WBC) count, hypoxemia, hypercapnia, acidosis, hyperkalemia, and elevated lactate, whereas late death was associated with a massive cytokine storm, a neutrophil-dominated WBC rebound/overshoot, increased lung oxidant injury, edema, and persistent ischemia. On day 6, seven of eight ALM survivors had inflammatory and immunological profiles not significantly different from those of sham-treated animals. We conclude in the rat model of experimental sepsis that small-volume ALM treatment led to higher survivability at 6 days (88%) than that of controls (25%). Early death in controls (day 2 to 3) was associated with significantly elevated plasma levels of IL-1β, IL-6, and C-reactive protein, severe plasma lymphocyte deficiency, reduced neutrophils, and acute lung injury. Late death (day 5) was associated with a massive neutrophil inflammatory storm, increased lung injury, and persistent ischemia. Possible mechanisms of ALM protection are discussed.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"23 11","pages":"863-872"},"PeriodicalIF":0.0,"publicationDate":"2016-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00390-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34353013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Natural Development of Antibodies against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis Protein Antigens during the First 13 Years of Life.","authors":"Igor C Borges,&nbsp;Dafne C Andrade,&nbsp;Maria Regina A Cardoso,&nbsp;Jorma Toppari,&nbsp;Mari Vähä-Mäkilä,&nbsp;Jorma Ilonen,&nbsp;Mikael Knip,&nbsp;Heikki Hyöty,&nbsp;Riitta Veijola,&nbsp;Olli Simell,&nbsp;Tuomas Jartti,&nbsp;Helena Käyhty,&nbsp;Olli Ruuskanen,&nbsp;Cristiana M Nascimento-Carvalho","doi":"10.1128/CVI.00341-16","DOIUrl":"https://doi.org/10.1128/CVI.00341-16","url":null,"abstract":"<p><p>Conserved protein antigens have been investigated as vaccine candidates against respiratory pathogens. We evaluated the natural development of antibodies against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis proteins during childhood. Serum samples were collected from 50 healthy children from their first months to age 13 years (median sampling interval, 6 months). We also analyzed serum samples from 24 adults. Serum IgG antibodies against eight pneumococcal proteins (Ply, CbpA, PspA 1 and 2, PcpA, PhtD, StkP-C, and PcsB-N), three H. influenzae proteins, and five M. catarrhalis proteins were measured using a multiplexed bead-based immunoassay. Antibody levels were analyzed using multilevel mixed-effects regression and Spearman's correlation. Antibody levels against pneumococcal proteins peaked at 3 to 5 years of age and then reached a plateau. Antibody levels against H. influenzae proteins peaked during the second year and then stabilized. Antibody levels against M. catarrhalis proteins peaked during the first year and then slowly decreased. Peak antibody levels during childhood were higher than those of adults. Correlations among pneumococcal antibody levels were highest among anti-CbpA, anti-PcpA, and anti-PhtD antibodies (r = 0.71 to 0.75; P < 0.001). The children presented 854 symptomatic respiratory infections on 586 occasions. Symptomatic respiratory infections did not improve prediction of antibody levels in the regression model. The maturation of immune responses against the investigated pneumococcal proteins shares similarities, especially among CbpA, PcpA, and PhtD. Antibody production against H. influenzae and M. catarrhalis proteins starts early in life and reaches peak levels earlier than antibody production against the pneumococcal proteins. Basal antibody levels are not related to the occurrence of symptomatic respiratory infections.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"23 11","pages":"878-883"},"PeriodicalIF":0.0,"publicationDate":"2016-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00341-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34353017","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic Neutralization of Pertussis Toxin by a Bispecific Antibody In Vitro and In Vivo.","authors":"Ellen K Wagner, Xianzhe Wang, Andre Bui, Jennifer A Maynard","doi":"10.1128/CVI.00371-16","DOIUrl":"10.1128/CVI.00371-16","url":null,"abstract":"<p><p>Bispecific antibodies are a rapidly growing class of therapeutic molecules, originally developed for the treatment of cancer but recently explored for the treatment of autoimmune and infectious diseases. Bordetella pertussis is a reemerging pathogen, and several of the key symptoms of infection are caused by the pertussis toxin (PTx). Two humanized antibodies, hu1B7 and hu11E6, bind distinct epitopes on PTx and, when coadministered, mitigate disease severity in murine and baboon models of infection. Here we describe the generation of a bispecific human IgG1 molecule combining the hu1B7 and hu11E6 binding sites via a knobs-in-holes design. The bispecific antibody showed binding activity equivalent to that of the antibody mixture in a competition enzyme-linked immunosorbent assay (ELISA). A CHO cell neutralization assay provided preliminary evidence for synergy between the two antibodies, while a murine model of PTx-induced leukocytosis definitively showed synergistic neutralization. Notably, the bispecific antibody retained the synergy observed for the antibody mixture, supporting the conclusion that synergy is due to simultaneous blockade of both the catalytic and receptor binding activities of pertussis toxin. These data suggest that a hu1B7/hu11E6 bispecific antibody is a viable alternative to an antibody mixture for pertussis treatment.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"23 11","pages":"851-862"},"PeriodicalIF":0.0,"publicationDate":"2016-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5098018/pdf/zcd851.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34353014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody Responses to Immunizations in Children with Type I Diabetes Mellitus: a Case-Control Study.","authors":"Michael Eisenhut,&nbsp;Alexander Chesover,&nbsp;Ronald Misquith,&nbsp;Nisha Nathwani,&nbsp;Andrew Walters","doi":"10.1128/CVI.00400-16","DOIUrl":"https://doi.org/10.1128/CVI.00400-16","url":null,"abstract":"<p><p>Type I diabetes mellitus (DM) has been associated with abnormalities of T cells. Our objective was to assess whether antibody responses to T-cell-dependent and -independent antigens in children with DM are lower than those of children without DM. We performed a case-control study matching children with DM to children without DM by age and by assessing antibody levels to pneumococcal serotypes, Haemophilus influenzae, and tetanus and diphtheria toxoids and reassessing antibody levels in patients with antibody levels below protective thresholds after booster immunization. We recruited 36 children with DM and 36 age-matched controls. The mean age was 10 years. There was no difference between groups in antibody levels against the antigens tested. Pneumococcal antibody levels below the protective threshold were found in 35.9% of DM patients after conjugate pneumococcal vaccination with no difference between groups. Booster immunization with unconjugated pneumococcal vaccine resulted in a median level against pneumococcal serotypes of 2.3 μg/ml (range, 0.05 to 664.7 μg/ml) in children with DM and 6.1 μg/ml (0.12 to 203.36 μg/ml) in children without DM (P = 0.013). Over 85% of children had levels above the protective threshold after booster immunization with no difference between groups. There was no evidence for a reduced antibody response to T-cell-dependent antigens given during childhood immunizations in children with DM. There was a reduced antibody response to antigens of pneumococcal strains in children with DM given unconjugated pneumococcal polysaccharide vaccine compared to that of children without DM without being associated with a difference in percentage of antibody levels below the protective threshold between groups.</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"23 11","pages":"873-877"},"PeriodicalIF":0.0,"publicationDate":"2016-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00400-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34353015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunogenicity of 13-Valent Conjugate Pneumococcal Vaccine in Patients 50 Years and Older with End-Stage Renal Disease and on Dialysis.","authors":"Subhashis Mitra,&nbsp;Gary E Stein,&nbsp;Shyam Bhupalam,&nbsp;Daniel H Havlichek","doi":"10.1128/CVI.00153-16","DOIUrl":"https://doi.org/10.1128/CVI.00153-16","url":null,"abstract":"<p><p>Patients with end-stage renal disease (ESRD) and on dialysis are at increased risk of pneumococcal disease. We evaluated the immunogenicity of the 13-valent pneumococcal conjugate vaccine (PCV13) in this population. Eligible patients with ESRD and on dialysis were given a single dose of PCV13. The concentrations of serum antibodies against 13 pneumococcal capsular polysaccharides were measured at the baseline and at 2 and 12 months postvaccination. A response to the vaccine was defined as a ≥2-fold increase in antibody concentration from that at the baseline and an absolute postvaccination value of at least 1 μg/ml. Seventeen patients completed the study. Increases in the concentrations of antibodies to the vaccine serotype were demonstrated 2 months after vaccination. The geometric mean antibody concentrations at 12 months postvaccination declined by 38% to 72% compared to those measured at 2 months postvaccination. A response to at least 1 serotype in the vaccine was seen in all patients at both 2 and 12 months postvaccination. The overall rate of the response to each individual vaccine serotype varied between 23.5% and 94.1% at 2 months postvaccination and 23.5% and 65% at 12 months postvaccination. Pain at the injection site was the most common local reaction. Vaccination with PCV13 induces antibody responses to vaccine serotypes in patients with ESRD and on dialysis at 2 months postvaccination. However, the decline in antibody concentrations at 12 months postvaccination with a conjugate pneumococcal vaccine requires further study. (This study has been registered at ClinicalTrials.gov under registration no. NCT01974817.).</p>","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"23 11","pages":"884-887"},"PeriodicalIF":0.0,"publicationDate":"2016-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1128/CVI.00153-16","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34353016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Superior Protection from Live-Attenuated Vaccines Directed against Johne's Disease","authors":"D. Shippy, Justin J. Lemke, A. Berry, Kathryn M. Nelson, M. Hines, A. Talaat","doi":"10.1128/CVI.00478-16","DOIUrl":"https://doi.org/10.1128/CVI.00478-16","url":null,"abstract":"ABSTRACT Mycobacterium avium subsp. paratuberculosis (M. paratuberculosis) is the etiological agent of Johne's disease in ruminants. Johne's disease is an important enteric infection causing large economic losses associated with infected herds. In an attempt to fight this infection, we created two novel live-attenuated vaccine candidates with mutations in sigH and lipN (pgsH and pgsN, respectively). Earlier reports in mice suggested these vaccines are promising candidates to fight Johne's disease in ruminants. In this study, we tested the performances of the two constructs as vaccine candidates using the goat model of Johne's disease. Both vaccines appeared to provide significant immunity to goats against challenge from wild-type M. paratuberculosis. The pgsH and pgsN constructs showed a significant reduction in histopathological lesions and tissue colonization compared to nonvaccinated goats and those vaccinated with an inactivated vaccine. Unlike the inactivated vaccine, the pgsN construct was able to eliminate fecal shedding from challenged animals, a feature that is highly desirable to control Johne's disease in infected herds. Furthermore, strong initial cell-mediated immune responses were elicited in goats vaccinated with pgsN that were not demonstrated in other vaccine groups. Overall, the results indicate the potential use of live-attenuated vaccines to control intracellular pathogens, including M. paratuberculosis, and warrant further testing in cattle, the main target for Johne's disease control programs.","PeriodicalId":10271,"journal":{"name":"Clinical and Vaccine Immunology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2016-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81689932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}