Therapeutic Advances in Vaccines and Immunotherapy最新文献

{"title":"<i>Neisseria meningitidis</i>: analysis of pili and LPS in emerging Brazilian strains.","authors":"Amanda Izeli Portilho, Gabriela Trzewikoswki de Lima, Elizabeth De Gaspari","doi":"10.1177/2515135520919195","DOIUrl":"10.1177/2515135520919195","url":null,"abstract":"<p><strong>Background: </strong><i>Neisseria meningitidis</i> is the main cause of bacterial meningitis in Brazil, where the main serogroups isolated are B and C; however, the serogroup W has recently emerged. LPS and type IV pili are important virulence factors that increase meningococci pathogenicity.</p><p><strong>Methods: </strong>The characterization of Lipopolysaccharide (LPS) and type IV pili in 19 meningococci strains of serogroup B, 21 of serogroup C, 45 of serogroup W and 28 of serogroup Y, isolated in Brazil between 2011 and 2017, was conducted using the Enzyme-linked Immunosorbent Assay (Dot- ELISA) technique and monoclonal antibodies.</p><p><strong>Results: </strong>We would like to emphasize the importance of characterizing relevant antigens, such as pili and LPS, the use of monoclonal antibodies to support it, and how such studies improve vaccine development and monitoring. Most of the strains studied presented L3,7,9 LPS and type IV pili; both antigens are associated with the capacity to cause invasive disease.</p><p><strong>Conclusion: </strong>Due to the impact of meningococcal disease, it is important to maintain and improve vaccine studies. Epitopes characterization provides data about the virulence of circulating strains. The use of monoclonal antibodies and serological techniques are relevant and support vaccine development.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"8 ","pages":"2515135520919195"},"PeriodicalIF":0.0,"publicationDate":"2020-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/76/fa/10.1177_2515135520919195.PMC7225800.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37960262","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":"Checkpoint inhibitor blockade and epigenetic reprogrammability in CD8⁺ T-cell activation and exhaustion.","authors":"José Belizário,&nbsp;Maria Fernanda Destro Rodrigues","doi":"10.1177/2515135520904238","DOIUrl":"https://doi.org/10.1177/2515135520904238","url":null,"abstract":"<p><p>CD8⁺ T-cell exhaustion is a dysfunctional state that is regulated through the expression of inhibitory checkpoint receptor genes including the cytotoxic T-lymphocyte-associated antigen 4, programmed death 1, and DNA methylation of effector genes interferon-γ, perforin, and granzyme B. Different strategies have been used to reverse T-cell exhaustion, which is an adverse event of checkpoint inhibitor blockade. Here, we present the mechanisms by which DNA methyltransferase inhibitors and Simian virus 40 large T antigen through viral mimicry can promote the reversion of exhausted CD8⁺ T cells. We examine how these pharmacological strategies can work together to improve the clinical efficacy of immunotherapies.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"8 ","pages":"2515135520904238"},"PeriodicalIF":0.0,"publicationDate":"2020-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135520904238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37766467","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":"Influenza vaccines: the potential benefits of cell-culture isolation and manufacturing.","authors":"Sankarasubramanian Rajaram,&nbsp;Constantina Boikos,&nbsp;Daniele K Gelone,&nbsp;Ashesh Gandhi","doi":"10.1177/2515135520908121","DOIUrl":"https://doi.org/10.1177/2515135520908121","url":null,"abstract":"<p><p>Influenza continues to cause severe illness in millions and deaths in hundreds of thousands annually. Vaccines are used to prevent influenza outbreaks, however, the influenza virus mutates and annual vaccination is required for optimal protection. Vaccine effectiveness is also affected by other potential factors such as the human immune system, a mismatch with the chosen candidate virus, and egg adaptation associated with egg-based vaccine production. This article reviews the influenza vaccine development process and describes the implications of the changes to the cell-culture process and vaccine strain recommendations by the World Health Organization since the 2017 season. The traditional manufacturing process for influenza vaccines relies on fertilized chicken eggs that are used for vaccine production. Vaccines must be produced in large volumes and the complete process requires approximately 6 months for the egg-based process. In addition, egg adaptation of seed viruses occurs when viruses adapt to avian receptors found within eggs to allow for growth in eggs. These changes to key viral antigens may result in antigenic mismatch and thereby reduce vaccine effectiveness. By contrast, cell-derived seed viruses do not require fertilized eggs and eliminate the potential for egg-adapted changes. As a result, cell-culture technology improves the match between the vaccine virus strain and the vaccine selected strain, and has been associated with increased vaccine effectiveness during a predominantly H3N2 season. During the 2017-2018 influenza season, a small number of studies conducted in the United States compared the effectiveness of egg-based and cell-culture vaccines and are described here. These observational and retrospective studies demonstrate that inactivated cell-culture vaccines were more effective than egg-based vaccines. Adoption of cell-culture technology for influenza vaccine manufacturing has been reported to improve manufacturing efficiency and the additional benefit of improving vaccine effectiveness is a key factor for future policy making considerations.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"8 ","pages":"2515135520908121"},"PeriodicalIF":0.0,"publicationDate":"2020-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135520908121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37702969","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":"Hepatitis B vaccine knowledge and self-reported vaccination status among healthcare workers in a conflict region in northeastern Nigeria.","authors":"Farouq Muhammad Dayyab,&nbsp;Garba Iliyasu,&nbsp;Bashir Garba Ahmad,&nbsp;Abdulaziz Tijjani Bako,&nbsp;Sepu Saraya Ngamariju,&nbsp;Abdulrazaq Garba Habib","doi":"10.1177/2515135519900743","DOIUrl":"https://doi.org/10.1177/2515135519900743","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis B virus (HBV) infection is highly endemic in Nigeria. The primary objective of this study is to describe the knowledge, self-reported vaccination status, and intention of healthcare workers to receive hepatitis B vaccine at a tertiary referral center in conflict-ravaged northeastern Nigeria.</p><p><strong>Methods: </strong>This was cross-sectional analytical study among medical practitioners, nurses, laboratory workers, health attendants, pharmacists, and radiographers working at Federal Medical Center Nguru, Yobe State. Written informed consent was obtained from all study participants. Data were obtained using questionnaires and entered into a Microsoft Excel spreadsheet, cleaned and analyzed using JMP Pro software.</p><p><strong>Results: </strong>Of the 182 participants, we found that 151 (82.97%), 81 (44.51%), 85 (46.70%), and 33 (18.13%) had good knowledge of HBV, good knowledge of hepatitis B vaccine, were vaccinated against HBV by the least dose, and had a complete hepatitis B vaccination status, respectively. The lack of availability of the vaccine was the main reason for not receiving the vaccine among the unvaccinated 36/91 (39.56%), followed by not knowing where to access the vaccine 19/91 (20.88%).</p><p><strong>Conclusion: </strong>The study highlights the need for strategies to ensure the availability of hepatitis B vaccine in conflict settings and need for vaccinology training given the suboptimal level of awareness and uptake of the hepatitis B vaccine among the healthcare workers.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"8 ","pages":"2515135519900743"},"PeriodicalIF":0.0,"publicationDate":"2020-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135519900743","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37596402","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":"Cross-reactivity with Brazilian strains of <i>Neisseria meningitidis</i> B after immunization with outer membrane vesicles.","authors":"Gabriela Trzewikoswki de Lima,&nbsp;Amanda Izeli Portilho,&nbsp;Elizabeth De Gaspari","doi":"10.1177/2515135519894825","DOIUrl":"https://doi.org/10.1177/2515135519894825","url":null,"abstract":"<p><strong>Background: </strong>Immunization against <i>Neisseria meningitidis</i> is important for public health. Vaccines composed of cross-reactivity antigens avoid strain-specific responses, ensuring more comprehensive protection.</p><p><strong>Methods: </strong>The cross-reactivity between three strains from the last outbreak of <i>N. meningitidis</i> in Brazil was assessed in our studies, using enzyme-linked immunosorbent assay (ELISA) and immunoblotting assays.</p><p><strong>Results: </strong>Both assays verifed a similar humoral response between the strains evaluated. Patterns of antigen recognition differed with each dose evaluated.</p><p><strong>Conclusions: </strong>We observed that immunization with <i>N. meningitidis</i> B outer membrane vesicles (OMVs) led to the production of antibodies that recognized antigens of heterologous strains, indicating possible protection against these evaluated strains.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"7 ","pages":"2515135519894825"},"PeriodicalIF":0.0,"publicationDate":"2019-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135519894825","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37471458","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":"Is a universal influenza vaccine feasible?","authors":"Joshua E Phillipson,&nbsp;Ron Babecoff,&nbsp;Tamar Ben-Yedidia","doi":"10.1177/2515135519885547","DOIUrl":"https://doi.org/10.1177/2515135519885547","url":null,"abstract":"<p><p>The influenza virus causes significant human morbidity and mortality annually and poses a pandemic threat. In addition, the virus frequently mutates, contributing to thousands of identified strains. Current influenza vaccine solutions are strain specific, target existing strains, and achieve only approximately 40% vaccine effectiveness (VE). The need for broadly protective Universal Influenza Vaccines (UIVs) is clear. UIV research and development efforts focus on widely conserved (i.e. not strain specific) influenza epitopes. The most clinically advanced UIV candidate, the Multimeric-001 (M-001), is currently undergoing a pivotal, clinical efficacy, phase III trial. Completed clinical trials indicate M-001 is safe, well tolerated, and immunogenic to a broad range of influenza strains. Additional candidates are also under development, supported by public and private funding. Research results suggest that it is only a matter of time until a broadly protective influenza vaccine is approved for licensure.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"7 ","pages":"2515135519885547"},"PeriodicalIF":0.0,"publicationDate":"2019-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135519885547","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39792359","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":"Alphavirus-based hepatitis C virus therapeutic vaccines: can universal helper epitopes enhance HCV-specific cytotoxic T lymphocyte responses?","authors":"Georgia Koutsoumpli, P. Ip, Ilona Schepel, B. Hoogeboom, A. Boerma, T. Daemen","doi":"10.1177/2515135519874677","DOIUrl":"https://doi.org/10.1177/2515135519874677","url":null,"abstract":"Background: Antigen-specific T cell immune responses play a pivotal role in resolving acute and chronic hepatitis C virus (HCV) infections. Currently, no prophylactic or therapeutic vaccines against HCV are available. We previously demonstrated the preclinical potency of therapeutic HCV vaccines based on recombinant Semliki Forest virus (SFV) replicon particles. However, clinical trials do not always meet the high expectations of preclinical studies, thus, optimization of vaccine strategies is crucial. In efforts to further increase the frequency of HCV-specific immune responses in the candidate SFV-based vaccines, the authors assessed whether inclusion of three strong, so-called universal helper T cell epitopes, and an endoplasmic reticulum localization, and retention signal (collectively termed sigHELP-KDEL cassette) could enhance HCV-specific immune responses. Methods: We included the sigHELP-KDEL cassette in two of the candidate SFV-based HCV vaccines, targeting NS3/4A and NS5A/B proteins. We characterized the new constructs in vitro for the expression and stability of the transgene-encoded proteins. Their immune efficacy with respect to HCV-specific immune responses in vivo was compared with the parental SFV vaccine expressing the corresponding HCV antigen. Further characterization of the functionality of the HCV-specific CD8+ T cells was assessed by surface and intracellular cytokine staining and flow cytometry analysis. Results: Moderate, but significantly, enhanced frequencies of antigen-specific immune responses were achieved upon lower/suboptimal dosage immunization. In optimal dosage immunization, the inclusion of the cassette did not further increase the frequencies of HCV-specific CD8+ T cells when compared with the parental vaccines and the frequencies of effector and memory populations were identical. Conclusion: We hypothesize that the additional effect of the sigHELP-KDEL cassette in SFV-based vaccines depends on the immunogenicity, nature, and stability of the target antigen expressed by the vaccine.","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135519874677","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43680743","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":"Seasonal influenza vaccination: knowledge, attitude and practice in Varna, Bulgaria","authors":"N. Ermenlieva, G. Tsankova, T. Todorova","doi":"10.1177/2515135519868152","DOIUrl":"https://doi.org/10.1177/2515135519868152","url":null,"abstract":"Background: Seasonal influenza vaccination is recommended for certain at-risk groups in Bulgaria, but vaccine coverage and the population’s perception of vaccination are currently unknown. The objective of this study was to assess the level of seasonal influenza vaccination in Varna Region, Bulgaria. It also aimed to investigate the status of knowledge and the attitude towards the reliability, safety, and other aspects associated with the use of influenza vaccines. Methods: A cross-sectional survey was conducted among 120 responders in Varna Region, Bulgaria. They completed a questionnaire assessing the practice, knowledge, and attitude towards seasonal influenza vaccination. Results: Nearly 70% of all responders have never been vaccinated against seasonal influenza in their lives. The main reason indicated was a lack of confidence in the vaccine in general (53.7% of nonvaccinated responders). Individuals with insufficient knowledge, or with a negative perception, were more likely to not be vaccinated: being poorly informed and having a negative attitude towards influenza vaccination also decreased the chance of being vaccinated by 29% and 36%, respectively. Conclusions: This study indicates that efforts should be made towards achieving better understanding and knowledge of the vaccine’s mechanism of prevention and effectiveness among the Bulgarian population.","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135519868152","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45280776","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":"Identification of goals and barriers to treatment from 92 consecutive consultations with families considering peanut oral immunotherapy.","authors":"Andrea C Blackman,&nbsp;Aikaterini Anagnostou","doi":"10.1177/2515135519869763","DOIUrl":"https://doi.org/10.1177/2515135519869763","url":null,"abstract":"<p><strong>Background: </strong>Peanut allergy has become an important public health issue. It can be the cause of severe reactions and also the trigger of significant anxiety for the allergic individual, especially with regards to the risk of unintentional accidental exposures. Peanut oral immunotherapy (POIT) is a newly developed treatment approach that has been shown to be highly effective in multiple research studies and has been associated with an acceptable safety profile. This treatment modality is likely to become more mainstream in the next few years with new commercial entities pursuing United States Food and Drug Administration approval for relevant products and multiple providers offering various forms of immunotherapy in their practices.</p><p><strong>Methods: </strong>The aim of our study was to obtain an accurate assessment of goals of treatment as well as concerns and barriers from families considering POIT in either the research or clinical setting. A single clinician allergist met with all the families and conducted semi-structured interviews on POIT. Families were provided with standardized written information on POIT prior to the consultation, which was used as a formalized instrument to communicate treatment protocols. Conversations were not recorded, but collected information was scribed by a second clinician who did not actively participate in the consultation. Scribed information was coded by the investigators. Thematic analysis identified common topics emerging from the discussions.</p><p><strong>Results: </strong>We report on the results of 92 consecutive family consultations on POIT conducted over a period of 1 year. Approximately 50% of the families had already researched POIT online, with 25% of families reported being part of Facebook parent groups. Groups identified the following areas as the most important considerations: efficacy, practical information, safety, benefits and goals, eligibility criteria and support in making the right decision. For all families pursuing POIT for their child, the initial goal was achieving protection from accidental exposure and cross-contamination and for approximately one-quarter, consumption of high peanut doses was the ultimate goal.</p><p><strong>Conclusion: </strong>Our research adds to the limited available data in this area and provides information that may be used as an initial platform for clinical consultations and shared decision-making in POIT. Obtaining a better understanding of patients' expectations and concerns will hopefully facilitate this process, enabling more fruitful and engaging interactions between families and healthcare providers in the field of food allergy.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"7 ","pages":"2515135519869763"},"PeriodicalIF":0.0,"publicationDate":"2019-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135519869763","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41214729","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":"Therapeutic vaccination immunomodulation: forming the basis of all cancer immunotherapy.","authors":"Brendon J Coventry","doi":"10.1177/2515135519862234","DOIUrl":"10.1177/2515135519862234","url":null,"abstract":"<p><p>Recent immunotherapy advances have convincingly demonstrated complete tumour removal with long-term survival. These impressive clinical responses have rekindled enthusiasm towards immunotherapy and tumour antigen vaccination providing 'cures' for melanoma and other cancers. However, many patients still do not benefit; sometimes harmed by severe autoimmune toxicity. Checkpoint inhibitors (anti-CTLA4; anti-PD-1) and interleukin-2 (IL-2) are 'pure immune drivers' of pre-existing immune responses and can induce either desirable effector-stimulatory or undesirable inhibitory-regulatory responses. Why some patients respond well, while others do not, is presently unknown, but might be related to the cellular populations being 'driven' at the time of dosing, dictating the resulting immune response. Vaccination is in-vivo immunotherapy requiring an active host response. Vaccination for cancer treatment has been skeptically viewed, arising partially from difficulty demonstrating clear, consistent clinical responses. However, this article puts forward accumulating evidence that 'vaccination' immunomodulation constitutes the fundamental, central, intrinsic property associated with antigen exposure not only from exogenous antigen (allogeneic or autologous) administration, but also from endogenous release of tumour antigen (autologous) from in-vivo tumour-cell damage and lysis. Many 'standard' cancer therapies (chemotherapy, radiotherapy etc.) create waves of tumour-cell damage, lysis and antigen release, thus constituting 'in-vivo vaccination' events. In essence, whenever tumour cells are killed, antigen release can provide in-vivo repeated vaccination events. Effective anti-tumour immune responses require antigen release/supply; immune recognition, and immune responsiveness. With better appreciation of endogenous vaccination and immunomodulation, more refined approaches can be engineered with prospect of higher success rates from cancer therapy, including complete responses and better survival rates.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"7 ","pages":"2515135519862234"},"PeriodicalIF":0.0,"publicationDate":"2019-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bf/36/10.1177_2515135519862234.PMC6676259.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41214730","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}