Journal of immune based therapies and vaccines最新文献

{"title":"HIV-1 sub-type C chimaeric VLPs boost cellular immune responses in mice.","authors":"Sirika Pillay,&nbsp;Enid G Shephard,&nbsp;Ann E Meyers,&nbsp;Anna-Lise Williamson,&nbsp;Edward P Rybicki","doi":"10.1186/1476-8518-8-7","DOIUrl":"https://doi.org/10.1186/1476-8518-8-7","url":null,"abstract":"<p><p> Several approaches have been explored to eradicate HIV; however, a multigene vaccine appears to be the best option, given their proven potential to elicit broad, effective responses in animal models. The Pr55Gag protein is an excellent vaccine candidate in its own right, given that it can assemble into large, enveloped, virus-like particles (VLPs) which are highly immunogenic, and can moreover be used as a scaffold for the presentation of other large non-structural HIV antigens. In this study, we evaluated the potential of two novel chimaeric HIV-1 Pr55Gag-based VLP constructs - C-terminal fusions with reverse transcriptase and a Tat::Nef fusion protein, designated GagRT and GagTN respectively - to enhance a cellular response in mice when used as boost components in two types of heterologous prime-boost vaccine strategies. A vaccine regimen consisting of a DNA prime and chimaeric HIV-1 VLP boosts in mice induced strong, broad cellular immune responses at an optimum dose of 100 ng VLPs. The enhanced cellular responses induced by the DNA prime-VLP boost were two- to three-fold greater than two DNA vaccinations. Moreover, a mixture of GagRT and GagTN VLPs also boosted antigen-specific CD8+ and CD4+ T-cell responses, while VLP vaccinations only induced predominantly robust Gag CD4+ T-cell responses. The results demonstrate the promising potential of these chimaeric VLPs as vaccine candidates against HIV-1.</p>","PeriodicalId":84998,"journal":{"name":"Journal of immune based therapies and vaccines","volume":"8 ","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2010-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1476-8518-8-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29477354","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":"Antiviral activity of Engystol® and Gripp-Heel®: an in-vitro assessment.","authors":"Kerstin Roeska,&nbsp;Bernd Seilheimer","doi":"10.1186/1476-8518-8-6","DOIUrl":"https://doi.org/10.1186/1476-8518-8-6","url":null,"abstract":"<p><strong>Background: </strong>Infections with respiratory viruses can activate the innate immune response - an important host defence mechanism in the early stage of viral infection. Interferon (IFN) release, triggered by virus infection, is an important factor in establishing an antiviral state, where IFN activation occurs prior to the onset of the adaptive immune response.The two ultra-low-dose combination medications, Engystol® and Gripp-Heel®, have documented efficacy for the treatment of the respiratory infections. However, the underlying antiviral mechanisms remain elusive.</p><p><strong>Methods: </strong>It was the goal to investigate whether Engystol® and Gripp-Heel® display antiviral activity in a prophylactic treatment protocol (2, 24 and 48 h pre-incubation) using a plaque reduction assay and whether the medications affect the release of type 1 IFN in virus-susceptible cell lines and human peripheral blood mononuclear cells (PBMCs).</p><p><strong>Results: </strong>Both medications demonstrate prophylactic effect against viral respiratory virus replication. However, when the incubation was continued for up to 5 days, both medications exhibited a pronounced antiviral effect which was dependent on the pre-incubation time. Moreover, in co-stimulated HeLa cells as well as in activated PBMCs Gripp-Heel® and Engystol® demonstrated an increased type 1 IFN production.</p><p><strong>Conclusions: </strong>Engystol® and Gripp-Heel® inhibited the replication of a variety of respiratory viruses. Additionally, we showed that pre-incubation affects the magnitude of the inhibitory effect differently for the various tested viruses. Both medications stimulate type 1 IFN release in different cell systems which suggests that their antiviral activity may be mediated possibly via modulation of the antiviral type 1 IFN host response.</p>","PeriodicalId":84998,"journal":{"name":"Journal of immune based therapies and vaccines","volume":"8 ","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2010-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1476-8518-8-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29471796","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":"Probing local innate immune responses after mucosal immunisation.","authors":"Lindsay J Hall,&nbsp;Simon Clare,&nbsp;Gordon Dougan","doi":"10.1186/1476-8518-8-5","DOIUrl":"https://doi.org/10.1186/1476-8518-8-5","url":null,"abstract":"<p><strong>Background: </strong>Intranasal immunisation is potentially a very effective route for inducing both mucosal and systemic immunity to an infectious agent.</p><p><strong>Methods: </strong>Balb/c mice were intranasally immunised with the mucosal adjuvant heat labile toxin and the Mycobacterium tuberculosis fusion protein Ag85B-ESAT6 and early changes in innate immune responses within local mucosal tissues were examined using flow cytometry and confocal microscopy. Antigen-specific humoral and cellular immune responses were also evaluated.</p><p><strong>Results: </strong>Intranasal immunisation induced significant changes in both number and distribution of dendritic cells, macrophages and neutrophils within the nasal-associated lymphoid tissue and cervical lymph nodes in comparison to controls as early as 5 h post immunisation. Immunisation also resulted in a rapid and transient increase in activation marker expression first in the nasal-associated lymphoid tissue, and then in the cervical lymph nodes. This heightened activation status was also apparent from the pro-inflammatory cytokine profiles of these innate populations. In addition we also showed increased expression and distribution of a number of different cell adhesion molecules early after intranasal immunisation within these lymphoid tissues. These observed early changes correlated with the induction of a TH1 type immune response.</p><p><strong>Conclusions: </strong>These data provide insights into the complex nature of innate immune responses induced following intranasal immunisation within the upper respiratory tract, and may help clarify the concepts and provide the tools that are needed to exploit the full potential of mucosal vaccines.</p>","PeriodicalId":84998,"journal":{"name":"Journal of immune based therapies and vaccines","volume":" ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2010-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1476-8518-8-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40065470","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":"PCEP enhances IgA mucosal immune responses in mice following different immunization routes with influenza virus antigens.","authors":"Nelson F Eng,&nbsp;Srinivas Garlapati,&nbsp;Volker Gerdts,&nbsp;Lorne A Babiuk,&nbsp;George K Mutwiri","doi":"10.1186/1476-8518-8-4","DOIUrl":"https://doi.org/10.1186/1476-8518-8-4","url":null,"abstract":"<p><strong>Background: </strong>We previously demonstrated that polyphosphazenes, particularly PCEP, enhance immune responses in mice immunized subcutaneously and intranasally. The objective of the present study was to investigate the efficacy of polyphosphazenes as adjuvants when delivered through different routes of vaccine administration.</p><p><strong>Methods: </strong>BALB/c mice were immunized through intranasal, subcutaneous, oral and intrarectal delivery with vaccine formulations containing either influenza X:31 antigen alone or formulated in PCEP. Serum and mucosal washes were collected and assayed for antigen-specific antibody responses by ELISA, while splenocytes were assayed for antigen-specific cytokine production by ELISPOT.</p><p><strong>Results: </strong>Intranasal immunization with PCEP+X:31 induced significantly higher IgA titers in all mucosal secretions (lung, nasal, and vaginal) compared to the other routes. Serum analysis showed that all mice given the PCEP+X:31 combination showed evidence of enhanced IgG2a titers in all administered routes, indicating that PCEP can be effective as an adjuvant in enhancing systemic immune responses when delivered via different routes of administration.</p><p><strong>Conclusions: </strong>We conclude that PCEP is a potent and versatile mucosal adjuvant that can be administered in a variety of routes and effectively enhances systemic and local immune responses. Furthermore, intranasal immunization was found to be the best administration route for enhancing IgA titers, providing further evidence for the potential of PCEP as a mucosal adjuvant.</p>","PeriodicalId":84998,"journal":{"name":"Journal of immune based therapies and vaccines","volume":"8 ","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2010-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1476-8518-8-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29212807","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":"Assessment of immune response to repeat stimulation with BCG vaccine using in vitro PBMC model.","authors":"Rajpal S Kashyap,&nbsp;Aliabbas A Husain,&nbsp;Shweta H Morey,&nbsp;Milind S Panchbhai,&nbsp;Poonam S Deshpande,&nbsp;Hemant J Purohit,&nbsp;Girdhar M Taori,&nbsp;Hatim F Daginawala","doi":"10.1186/1476-8518-8-3","DOIUrl":"https://doi.org/10.1186/1476-8518-8-3","url":null,"abstract":"<p><strong>Background: </strong>Tuberculosis (TB) is one of the most prevalent cause of death due to a single pathogen. Bacillus Calmette Guérin (BCG) is the only vaccine available for clinical use that protects against miliary TB; however, this vaccine has shown variable levels of efficacy against pulmonary TB. In India, a single dose of BCG vaccine is given and there are few countries where repeated doses of BCG are given. The incidence of TB in India is very high inspite of primary vaccination in neonatal period and therefore requires consideration for repeated immunization.</p><p><strong>Methods: </strong>To improve BCG immunogenicity, we have evaluated specific antimycobacterial immune responses (anti-BCG IgG and IFN-gamma), T cell activity-ADA, CD4 and CD8 T cell count, and CD4/CD8 ratio in a peripheral blood mononuclear cells (PBMC) model using boost immunization protocols with the BCG vaccine. PBMC were induced with a repeat dose of BCG at 24 and 72 hrs of cell culture.</p><p><strong>Results: </strong>At the end of the experimental time, supernatant was collected to estimate anti-BCG IgG titer, interferon gamma, ADA activity, CD 4 and CD8 T cell count, and CD4/CD8 ratio. We demonstrated that PBMC induced with a repeat dose of BCG showed an increased specific anti-mycobacterial immune responses, T cell activity, and ADA activity as compared to PBMC induced with BCG alone or without BCG induction.</p><p><strong>Conclusion: </strong>The repeat BCG stimulation of PBMC obtained from BCG vaccinated individuals shows enhanced immune activation with respect to increased anti-BCG titre, IFN-gamma and ADA activity without concomitant increase in CD4 and CD8 cells. This study provides some basic data in future experiments in animal models with respect to repeat BCG vaccination.</p>","PeriodicalId":84998,"journal":{"name":"Journal of immune based therapies and vaccines","volume":"8 ","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2010-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1476-8518-8-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29023135","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":"CpG oligodeoxyribonucleotides protect mice from Burkholderia pseudomallei but not Francisella tularensis Schu S4 aerosols.","authors":"David A Rozak,&nbsp;Herbert C Gelhaus,&nbsp;Mark Smith,&nbsp;Mojgan Zadeh,&nbsp;Louis Huzella,&nbsp;David Waag,&nbsp;Jeffrey J Adamovicz","doi":"10.1186/1476-8518-8-2","DOIUrl":"https://doi.org/10.1186/1476-8518-8-2","url":null,"abstract":"<p><p> Studies have shown that CpG oligodeoxyribonucleotides (ODN) protect mice from various bacterial pathogens, including Burkholderia pseudomallei and Francisella tularensis live vaccine strain (LVS), when administered before parenteral challenge. Given the potential to develop CpG ODN as a pre-treatment for multiple bacterial biological warfare agents, we examined survival, histopathology, and cytokine data from CpG ODN-treated C57BL/6 mice to determine whether previously-reported protection extended to aerosolized B. pseudomallei 1026b and highly virulent F. tularensis Schu S4 infections. We found that, although CpG ODN protected mice from aerosolized B. pseudomallei challenges, the immunostimulant failed to benefit the animals exposed to F. tularensis Schu S4 aerosols. Our results, which contrast with earlier F. tularensis LVS studies, highlight potential differences in Francisella species pathogenesis and underscore the need to evaluate immunotherapies against human pathogenic species.</p>","PeriodicalId":84998,"journal":{"name":"Journal of immune based therapies and vaccines","volume":"8 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2010-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1476-8518-8-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28735029","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":"CD40mAb adjuvant induces a rapid antibody response that may be beneficial in post-exposure prophylaxis.","authors":"Vijay Ns Bhagawati-Prasad,&nbsp;Evy De Leenheer,&nbsp;Nadine P Keefe,&nbsp;Lorna A Ryan,&nbsp;Jennifer Carlring,&nbsp;Andrew W Heath","doi":"10.1186/1476-8518-8-1","DOIUrl":"https://doi.org/10.1186/1476-8518-8-1","url":null,"abstract":"<p><p> Active vaccination can be effective as a post-exposure prophylaxis, but the rapidity of the immune response induced, relative to the incubation time of the pathogen, is critical. We show here that CD40mAb conjugated to antigen induces a more rapid specific antibody response than currently used immunological adjuvants, alum and monophosphoryl lipid A.</p>","PeriodicalId":84998,"journal":{"name":"Journal of immune based therapies and vaccines","volume":"8 ","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2010-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1476-8518-8-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28755900","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":"HIV-1 neutralization by monoclonal antibody against conserved region 2 and patterns of epitope exposure on the surface of native viruses.","authors":"Apichai Sreepian,&nbsp;Jongruk Permmongkol,&nbsp;Wannee Kantakamalakul,&nbsp;Sontana Siritantikorn,&nbsp;Nattaya Tanlieng,&nbsp;Ruengpung Sutthent","doi":"10.1186/1476-8518-7-5","DOIUrl":"https://doi.org/10.1186/1476-8518-7-5","url":null,"abstract":"<p><strong>Background: </strong>Conserved neutralizing epitopes are considered to be a key role for eliciting broadly neutralizing antibody (NAb). Previously, two conserved neutralizing epitopes of HIV-1 CRF01_AE envelope were identified at amino acid 93-112 of the C1 (C1E) and at 218-239 of the C2 (C2E) regions. To access the potency of antibody directed against conserved epitopes, a monoclonal antibody (MAb) specific to the C2E region was developed and characterized.</p><p><strong>Methods: </strong>The immunogenicity of two epitopes was examined by immunizing BALB/c mice with the matching synthetic peptides. One MAb, C2EB5, directed against peptide C2E, was generated by conventional methods, while C1E1 and C1E2 peptides induced slight antibody response in mice. The neutralizing activity of MAb C2EB5 was examined using a peripheral blood mononuclear cell (PBMC) based method and various HIV-1 subtypes including A, B, C, D, and CRF01_AE; C2EB5 was compared with other known neutralizing MAbs (4E10, 447-52D) and with sCD4. The exposure of the C2 epitope on native virus was investigated using virus capture by these MAbs.</p><p><strong>Results: </strong>The MAb C2EB5 demonstrated cross-neutralization against various HIV-1 subtypes. The overall potency of MAb C2EB5 against 5 subtypes was ranked in the following order: subtype C> CRF01_AE> subtype D> subtype A> subtype B. The epitope exposure for MAb C2EB5 was also correlated with the neutralization properties of each subtype.</p><p><strong>Conclusion: </strong>This study demonstrates the cross-clade neutralizing activity of a MAb directed against an epitope located in the C2 region of the HIV-1 env and highlights differences in the exposure of antigenic epitopes on the surface of various HIV-1 subtypes. The epitope for this newly identified neutralizing MAb made against a subtype CRF01_AE peptide is particularly exposed in subtype C viral isolates.</p>","PeriodicalId":84998,"journal":{"name":"Journal of immune based therapies and vaccines","volume":"7 ","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2009-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1476-8518-7-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28430378","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":"DNA vaccine containing the mycobacterial hsp65 gene prevented insulitis in MLD-STZ diabetes.","authors":"Rubens R Santos,&nbsp;Alexandrina Sartori,&nbsp;Deison S Lima,&nbsp;Patrícia Rm Souza,&nbsp;Arlete Am Coelho-Castelo,&nbsp;Vânia Ld Bonato,&nbsp;Célio L Silva","doi":"10.1186/1476-8518-7-4","DOIUrl":"https://doi.org/10.1186/1476-8518-7-4","url":null,"abstract":"<p><strong>Background: </strong>Our group previously demonstrated that a DNA plasmid encoding the mycobacterial 65-kDa heat shock protein (DNA-HSP65) displayed prophylactic and therapeutic effect in a mice model for tuberculosis. This protection was attributed to induction of a strong cellular immunity against HSP65. As specific immunity to HSP60 family has been detected in arthritis, multiple sclerosis and diabetes, the vaccination procedure with DNA-HSP65 could induce a cross-reactive immune response that could trigger or worsen these autoimmune diseases.</p><p><strong>Methods: </strong>In this investigation was evaluated the effect of a previous vaccination with DNA-HSP65 on diabetes development induced by Streptozotocin (STZ). C57BL/6 mice received three vaccine doses or the corresponding empty vector and were then injected with multiple low doses of STZ.</p><p><strong>Results: </strong>DNA-HSP65 vaccination protected mice from STZ induced insulitis and this was associated with higher production of IL-10 in spleen and also in the islets. This protective effect was also concomitant with the appearance of a regulatory cell population in the spleen and a decreased infiltration of the islets by T CD8+ lymphocytes. The vector (DNAv) also determined immunomodulation but its protective effect against insulitis was very discrete.</p><p><strong>Conclusion: </strong>The data presented in this study encourages a further investigation in the regulatory potential of the DNA-HSP65 construct. Our findings have important implications for the development of new immune therapy strategies to combat autoimmune diseases.</p>","PeriodicalId":84998,"journal":{"name":"Journal of immune based therapies and vaccines","volume":"7 ","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2009-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/1476-8518-7-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28475787","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":"Prospects for control of emerging infectious diseases with plasmid DNA vaccines.","authors":"Ronald B Moss","doi":"10.1186/1476-8518-7-3","DOIUrl":"10.1186/1476-8518-7-3","url":null,"abstract":"<p><p> Experiments almost 20 years ago demonstrated that injections of a sequence of DNA encoding part of a pathogen could stimulate immunity. It was soon realized that \"DNA vaccination\" had numerous potential advantages over conventional vaccine approaches including inherent safety and a more rapid production time. These and other attributes make DNA vaccines ideal for development against emerging pathogens. Recent advances in optimizing various aspects of DNA vaccination have accelerated this approach from concept to reality in contemporary human trials. Although not yet licensed for human use, several DNA vaccines have now been approved for animal health indications. The rapid manufacturing capabilities of DNA vaccines may be particularly important for emerging infectious diseases including the current novel H1N1 Influenza A pandemic, where pre-existing immunity is limited. Because of recent advances in DNA vaccination, this approach has the potential to be a powerful new weapon in protecting against emerging and potentially pandemic human pathogens.</p>","PeriodicalId":84998,"journal":{"name":"Journal of immune based therapies and vaccines","volume":"7 ","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2009-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2746192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28388038","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}