Therapeutic Advances in Vaccines and Immunotherapy最新文献

{"title":"Evaluation of immunogenicity, safety and breakthrough following administration of live attenuated varicella vaccine in two doses three months apart regimen in Indian children.","authors":"Monjori Mitra, Jaydeep Chowdhury, Surupa Basu, Partha Pratim Halder, Mallar Mukherjee, Archana Karadkhele, Gaurav Puppalwar, Rishi Jain","doi":"10.1177/2515135520937216","DOIUrl":"10.1177/2515135520937216","url":null,"abstract":"<p><strong>Background: </strong>In India, where varicella outbreaks are reported at a younger age, a two-dose vaccine schedule administered at an early age could be highly efficacious in preventing varicella infection. The aim of this study was to evaluate the immunogenicity and safety of live attenuated varicella vaccine (VR 795 Oka strain) in a two-dose, 3 months apart regimen.</p><p><strong>Methodology: </strong>Healthy children (⩾ 12 months and ⩽12 years; mean age: 4.4 years) of either sex were included. Geometric mean titers (GMT) were measured at baseline and 28 days post first- and second-dose, and seroprotection rates were measured 28 days post first and second dose. The incidence of breakthrough (BT) infections post vaccination was determined from 42 days post first and second dose of vaccine up to 12 months. Adverse events (AEs) were monitored and recorded throughout the study period.</p><p><strong>Results: </strong>Of 305 subjects enrolled, 217 were seronegative. The seroconversion rate (a change from a seronegative to a seropositive condition) was 93.3% post first-dose and 100% post two-doses. High levels (9 times) of GMT were reported since post first-dose to post second-dose in children aged 12-18 months, 18-60 months (99.43%); and in and above 60 months (99.02%). The extent of rise of anti-VZV IgG antibody titer post 28 days of first-dose at two-fold, three-fold and four-fold rise was 93.39%, 90.56% and 80.66%, respectively and 100% 4-fold rise post second-dose. A single case, a day after the first-dose of vaccination of mild BT infection, was observed after close contact with a severe case. AEs were mild and none of the serious AEs were related to the study drug.</p><p><strong>Conclusion: </strong>The two-dose schedule of varicella vaccine was safe and immunogenic when given 3 months apart. However, further comparative studies and follow up for both dosing schedules are needed to validate the advantage of early dosing.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"8 ","pages":"2515135520937216"},"PeriodicalIF":0.0,"publicationDate":"2020-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/84/55/10.1177_2515135520937216.PMC7425319.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38314199","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":"COVID-19: should oral vaccination strategies be given more consideration?","authors":"Aman Mehan,&nbsp;Ashwin Venkatesh,&nbsp;Milind Girish","doi":"10.1177/2515135520946503","DOIUrl":"https://doi.org/10.1177/2515135520946503","url":null,"abstract":"Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). The novel coronavirus, SARS-CoV-2, has led to an unprecedented international health crisis. The implementation of a vaccine is essential to accelerate herd immunity, enabling lockdown measures to be relaxed and socioeconomic activity to safely resume whilst limiting the case fatality rate. A concerted global effort has led to over 150 vaccines currently under development. However, it is apparent that oral administration has been markedly under addressed as a potentially effective immunological strategy.","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"8 ","pages":"2515135520946503"},"PeriodicalIF":0.0,"publicationDate":"2020-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135520946503","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38259188","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":"Profile of adverse events following immunization with measles rubella vaccine at a tertiary care hospital in East Delhi, India.","authors":"Eshita Bhowmik,&nbsp;Aaradhana Singh,&nbsp;Ravi Sachan","doi":"10.1177/2515135520940131","DOIUrl":"https://doi.org/10.1177/2515135520940131","url":null,"abstract":"<p><strong>Background: </strong>As a part of a measles and rubella (MR) campaign, the MR vaccine replaced the two-dose measles vaccine at 9-12 months and 16-24 months of age under the Universal Immunization Program (UIP). Although adverse events following immunization (AEFIs) following the measles and MMR vaccine at 9 months of age have been studied, AEFIs following the MR vaccine at 9 months of age have not been studied. As the MR vaccine a is very recent introduction in the UIP for routine immunization at 9 months of age, we intend to investigate the AEFI profile of MR vaccination at 9 months of age by active surveillance.</p><p><strong>Aim: </strong>We aimed to study the profile of the AEFIs with MR vaccine at 9-12 months of age in children vaccinated at the immunization clinic at the Pediatrics Department of a tertiary care hospital in East Delhi, India.</p><p><strong>Methods: </strong>Our study was a prospective observational study (telephonic survey). Children who attended Pediatrics OPD for the first dose of the MR vaccine at 9-12 months of age were enrolled in the study. Demographic details of the children who received the first dose of MR vaccine at 9-12 months of age at the immunization clinic of the hospital were recorded in a case record form. A telephone survey was conducted on day 7 and day 30 post-vaccination for AEFIs.</p><p><strong>Result: </strong>A total of 278 children were enrolled in the study, but 7 were unavailable for the further telephone survey. A total of 42 (15.5%) AEFIs were reported, of which 39 (94%) were in the initial 7 days and 3 (6%) were in the following 21 days following immunization. Of the AEFIs reported, the most common symptom was fever (38%), followed by upper respiratory tract infection (30.9%), local swelling at injection site (26.1%), and skin rash (4%).</p><p><strong>Conclusion: </strong>MR vaccine introduced in National Immunization Schedule is found to be safe for use in children except for a few minor reactions.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"8 ","pages":"2515135520940131"},"PeriodicalIF":0.0,"publicationDate":"2020-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135520940131","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38177559","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":"Development of vaccines against the sexually transmitted infections gonorrhoea, syphilis, Chlamydia, herpes simplex virus, human immunodeficiency virus and Zika virus.","authors":"Edwin David G McIntosh","doi":"10.1177/2515135520923887","DOIUrl":"https://doi.org/10.1177/2515135520923887","url":null,"abstract":"<p><p>The success in preventing hepatitis B virus and human papillomavirus infections by means of vaccination paves the way for the development of other vaccines to prevent sexually transmitted infections (STIs) such as gonorrhoea, syphilis, chlamydia, herpes simplex virus, human immunodeficiency virus and Zika virus. The current status of vaccine development for these infections will be explored in this review. The general principles for success include the need for prevention of latency, persistence and repeat infections. A reduction in transmission of STIs would reduce the global burden of disease. Therapeutic activity of vaccines against STIs would be advantageous over preventative activity alone, and prevention of congenital and neonatal infections would be an added benefit. There would be an added value in the prevention of long-term consequences of STIs. It may be possible to re-purpose 'old' vaccines for new indications. One of the major challenges is the determination of the target populations for STI vaccination.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"8 ","pages":"2515135520923887"},"PeriodicalIF":0.0,"publicationDate":"2020-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135520923887","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38144339","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":"Transgenic T-cell receptor immunotherapy for cancer: building on clinical success.","authors":"Natasha Oppermans,&nbsp;Gray Kueberuwa,&nbsp;Robert E Hawkins,&nbsp;John S Bridgeman","doi":"10.1177/2515135520933509","DOIUrl":"https://doi.org/10.1177/2515135520933509","url":null,"abstract":"<p><p>With the advent of immunotherapy as a realistic and promising option for cancer treatment, adoptive cellular therapies are gaining significant interest in the clinic. Whilst the recent successes of chimeric antigen receptor T-cell therapies for haematological malignancies are widely known, they have yet to show great success in solid cancers. However, immune cells transduced with T-cell receptors have been shown to traffic to and exert anti-cancer effects on solid tumour cells with some great successes. In this review, we explore the field of transgenic T-cell receptor immunotherapy, highlighting some of the key clinical trials which have paved the way for this type of cellular immunotherapy. Some trials have shown amazing clinical results, including long-term remissions and minimal toxicity, and can be looked at as an exemplar for this adoptive cell therapy. There have also been key trials where unexpected, fatal, off-tumour toxicity has occurred, and these trials have also been instrumental in shaping safer clinical trials, particularly regarding preclinical testing. In addition to previous trials, we analysed the current clinical trial space for T-cell receptor T-cell therapy, showing which trials are dominating in the clinic and which targets are being prioritised by researchers around the world. By looking at both past and current trials, we have been able to identify key drivers in developing transgenic T-cell receptor immunotherapy for the future.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"8 ","pages":"2515135520933509"},"PeriodicalIF":0.0,"publicationDate":"2020-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135520933509","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38114581","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":"CAR T-cell immunotherapy of B-cell malignancy: the story so far.","authors":"Leena Halim, John Maher","doi":"10.1177/2515135520927164","DOIUrl":"10.1177/2515135520927164","url":null,"abstract":"<p><p>Chimeric antigen receptor (CAR) T-cell immunotherapy has achieved unprecedented efficacy in the treatment of chemotherapy-resistant or refractory B-cell malignancies. Promising results from pivotal anti-CD19 CAR T-cell phase II trials have led to landmark approvals of two CD19-specific CAR T-cell products by the United States Food and Drug Administration and European Medicines Agency. However, several issues associated with CAR T-cell treatment remain unresolved, such as the management of severe toxicities and the frequent occurrence of both antigen-positive and antigen-negative relapse. Nonetheless, pre-clinical research is advancing at an unprecedented pace to develop innovative solutions to address these issues. Herein, we summarise recent clinical developments and outcomes of CD19-targeted CAR T-cell immunotherapy and discuss emerging strategies that may further improve the success, safety and broadened applicability of this approach.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"8 ","pages":"2515135520927164"},"PeriodicalIF":0.0,"publicationDate":"2020-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/56/2e/10.1177_2515135520927164.PMC7257863.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38031872","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":"Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a double blind, phase III randomized clinical trial in healthy Serbian adults.","authors":"Goran Stevanovic,&nbsp;Aleksandar Obradovic,&nbsp;Snezana Ristic,&nbsp;Dragan Petrovic,&nbsp;Branislava Milenkovic,&nbsp;Danilo Mitrovic,&nbsp;Svetlana Filipovic Vignjevic,&nbsp;Katarina Ilic,&nbsp;Vera Stoiljkovic,&nbsp;Lidija Lavadinovic,&nbsp;Mijomir Pelemis,&nbsp;Svetlana Petrovic,&nbsp;Ana Vidmanic,&nbsp;Olga Popovic,&nbsp;Natasa Eremic,&nbsp;Erin Sparrow,&nbsp;Guido Torelli,&nbsp;Muriel Socquet,&nbsp;Renée Holt,&nbsp;Yordanka Ilieva-Borisova,&nbsp;Yuxiao Tang,&nbsp;Francesco Berlanda Scorza,&nbsp;Jorge Flores,&nbsp;Niraj Rathi","doi":"10.1177/2515135520925336","DOIUrl":"https://doi.org/10.1177/2515135520925336","url":null,"abstract":"<p><p>This study was a phase III, multicenter, double-blind, randomized, placebo-controlled trial to evaluate the safety and immunogenicity of a seasonal trivalent split, inactivated influenza vaccine (TIV) in healthy Serbian adults between the ages of 18 and 65 years. This egg-based vaccine was manufactured by the Institute of Virology, Vaccines and Sera, Torlak, Belgrade, Serbia. A total of 480 participants were assigned randomly in a ratio of 2:1 to receive a single intramuscular dose (0.5 ml) of the vaccine (15 µg of hemagglutinin per strain) or placebo (phosphate-buffered saline). Participants were monitored for safety, including solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs). No SAEs related to vaccination were reported. Injection site pain (51.3%), injection site tenderness (40.4%), tiredness (17.0%), and headache (15.1%) were the most commonly reported solicited events in the vaccine group. Incidence of related unsolicited AEs was low (1.3%) among vaccinees. Hemagglutinin inhibition (HAI) titers were measured before and 21 days after vaccination in 151 participants. Overall, HAI seroconversion rates to H1 and H3 were observed in 90.1% and 76.2% of vaccinees, respectively. For B antigen, it was 51.5%, likely due to high pre-vaccination titers. Post-vaccination seroprotection rates were in the range of 78.2-95.0% for the three antigens. Post-vaccination geometric mean titers (GMT) were at least 3.8 times higher than baseline levels for all the three strains among vaccinees. Overall, the study showed that the vaccine was safe and well tolerated, and induced a robust immune response against all three vaccine strains. ClinicalTrials.gov identifier: NCT02935192, October 17, 2016.</p>","PeriodicalId":33285,"journal":{"name":"Therapeutic Advances in Vaccines and Immunotherapy","volume":"8 ","pages":"2515135520925336"},"PeriodicalIF":0.0,"publicationDate":"2020-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/2515135520925336","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38027493","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":"<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}