NPJ Vaccines最新文献

{"title":"FcRn regulates antigen presentation in dendritic cells downstream of DEC205-targeted vaccines","authors":"Christophe Macri, Matthew Paxman, Devi Jenika, Xiao Peng Lin, Zahra Elahi, Paul A. Gleeson, Irina Caminschi, Mireille H. Lahoud, Jose A. Villadangos, Justine D. Mintern","doi":"10.1038/s41541-024-00854-8","DOIUrl":"https://doi.org/10.1038/s41541-024-00854-8","url":null,"abstract":"<p>Dendritic cell (DC)-targeted vaccination is a new mode of antigen delivery that relies on the use of monoclonal antibodies (mAb) to target antigen to specific DC subsets. The neonatal Fc receptor (FcRn) is a non-classical Fc receptor that binds to immunoglobulin G (IgG) in acidified endosomes and controls its intracellular transport and recycling. FcRn is known to participate in the antigen presentation of immune complexes, however its contribution to DC-targeted vaccination has not previously been examined. Here we have investigated the role of FcRn in antigen presentation using antigen conjugated to IgG mAb which target specific DC receptors, including DEC205 and Clec9A expressed by the conventional DC 1 (cDC1) subset. We show that FcRn is expressed at high levels by cDC1, both at steady-state and following activation and plays a significant role in MHC I cross-presentation and MHC II presentation of antigens that are targeted to cDC1 via mAb specific for DEC205. This effect of FcRn is intrinsic to cDC1 and FcRn impacts the efficacy of anti-DEC205-mediated vaccination against B cell lymphoma. In contrast, FcRn does not impact presentation of antigens targeted to Clec9A and does not regulate presentation of cell-associated antigen. These data highlight a new and unique role of FcRn in controlling the immunogenicity of anti-DEC205-based vaccination, with consequences for exploiting this pathway to improve DC-targeted vaccine outcomes.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recovery from antibody-mediated biliary ductopenia and multiorgan inflammation after COVID-19 vaccination","authors":"Alan Chang, Yung-Ming Jeng, Cheng-Maw Ho, Po-Huang Lee","doi":"10.1038/s41541-024-00861-9","DOIUrl":"https://doi.org/10.1038/s41541-024-00861-9","url":null,"abstract":"<p>The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality. Spike messenger RNA (mRNA)–based vaccines against severe acute respiratory syndrome coronavirus 2 may contribute to immune-mediated injuries. Here we present a case of a previously healthy 47-year-old man, who developed progressive jaundice 2 weeks after receiving his 3^rd COVID-19 vaccination (1^st mRNA-based vaccine). Apart from elevated serum total bilirubin levels (peaked at &gt;70 mg/dL), deteriorating renal (blood urea nitrogen: peak, 108.5 mg/dL; creatinine: peak, 6 mg/dL) and exocrine pancreas (amylase: peak, 1717 U/L; lipase: peak, 5784 U/L) profiles were also seen. Vanishing bile duct syndrome characterized by ductopenia and cholangiocyte vacuolation, positive C4d deposition, and high titer of anti-angiotensin II type 1 receptor antibody consistently explain the overall antibody-mediated pathogenesis resembling antibody-mediated “rejection” in the solid organ transplant setting. Corticosteroids and plasmapheresis were administered, leading to gradual resolution of the symptoms, and the jaundice completely resolved 2 months later. In conclusion, we reported a case of antibody-mediated multiorgan injury after an mRNA COVID-19 vaccine, characterized by severe cholangiopathy. The patient recovered with corticosteroids and plasmapheresis, and long-term follow-up is necessary.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Triple tandem trimer immunogens for HIV-1 and influenza nucleic acid-based vaccines","authors":"Iván del Moral-Sánchez, Edmund G. Wee, Yuejiao Xian, Wen-Hsin Lee, Joel D. Allen, Alba Torrents de la Peña, Rebeca Fróes Rocha, James Ferguson, André N. León, Sylvie Koekkoek, Edith E. Schermer, Judith A. Burger, Sanjeev Kumar, Robby Zwolsman, Mitch Brinkkemper, Aafke Aartse, Dirk Eggink, Julianna Han, Meng Yuan, Max Crispin, Gabriel Ozorowski, Andrew B. Ward, Ian A. Wilson, Tomáš Hanke, Kwinten Sliepen, Rogier W. Sanders","doi":"10.1038/s41541-024-00862-8","DOIUrl":"https://doi.org/10.1038/s41541-024-00862-8","url":null,"abstract":"<p>Recombinant native-like HIV-1 envelope glycoprotein (Env) trimers are used in candidate vaccines aimed at inducing broadly neutralizing antibodies. While state-of-the-art SOSIP or single-chain Env designs can be expressed as native-like trimers, undesired monomers, dimers and malformed trimers that elicit non-neutralizing antibodies are also formed, implying that these designs could benefit from further modifications for gene-based vaccination approaches. Here, we describe the triple tandem trimer (TTT) design, in which three Env protomers are genetically linked in a single open reading frame and express as native-like trimers. Viral vectored Env TTT induced similar neutralization titers but with a higher proportion of trimer-specific responses. The TTT design was also applied to generate influenza hemagglutinin (HA) trimers without the need for trimerization domains. Additionally, we used TTT to generate well-folded chimeric Env and HA trimers that harbor protomers from three different strains. In summary, the TTT design is a useful platform for the design of HIV-1 Env and influenza HA immunogens for a multitude of vaccination strategies.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"COVID-19 vaccination induces distinct T-cell responses in pediatric solid organ transplant recipients and immunocompetent children","authors":"Katerina Roznik, Jiashu Xue, Georgia Stavrakis, T. Scott Johnston, Divya Kalluri, Rivka Ohsie, Caroline X. Qin, John McAteer, Dorry L. Segev, Douglas Mogul, William A. Werbel, Andrew H. Karaba, Elizabeth A. Thompson, Andrea L. Cox","doi":"10.1038/s41541-024-00866-4","DOIUrl":"https://doi.org/10.1038/s41541-024-00866-4","url":null,"abstract":"<p>Immune responses to COVID-19 vaccination are attenuated in adult solid organ transplant recipients (SOTRs) and additional vaccine doses are recommended for this population. However, whether COVID-19 mRNA vaccine responses are limited in pediatric SOTRs (pSOTRs) compared to immunocompetent children is unknown. Due to SARS-CoV-2 evolution and mutations that evade neutralizing antibodies, T cells may provide important defense in SOTRs who mount poor humoral responses. Therefore, we assessed anti-SARS-CoV-2 IgG titers, surrogate neutralization, and spike (S)-specific T-cell responses to COVID-19 mRNA vaccines in pSOTRs and their healthy siblings (pHCs) before and after the bivalent vaccine dose. Despite immunosuppression, pSOTRs demonstrated humoral responses to both ancestral strain and Omicron subvariants following the primary ancestral strain monovalent mRNA COVID-19 series and multiple booster doses. These responses were not significantly different from those observed in pHCs and significantly higher six months after vaccination than responses in adult SOTRs two weeks post-vaccination. However, pSOTRs mounted limited S-specific CD8⁺ T-cell responses and qualitatively distinct CD4⁺ T-cell responses, primarily producing IL-2 and TNF with less IFN-γ production compared to pHCs. Bivalent vaccination enhanced humoral responses in some pSOTRs but did not shift the CD4⁺ T-cell responses toward increased IFN-γ production. Our findings indicate that S-specific CD4⁺ T cells in pSOTRs have distinct qualities with unknown protective capacity, yet vaccination produces cross-reactive antibodies not significantly different from responses in pHCs. Given altered T-cell responses, additional vaccine doses in pSOTRs to maintain high titer cross-reactive antibodies may be important in ensuring protection against SARS-CoV-2.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potent and long-lasting humoral and cellular immunity against varicella zoster virus induced by mRNA-LNP vaccine","authors":"Anannya Bhattacharya, Lonzaric Jan, Olga Burlak, Jilong Li, Ghanshyam Upadhyay, Katherine Williams, Jinhui Dong, Harrison Rohrer, Michelle Pynn, Andrew Simon, Nathan Kuhlmann, Sergei Pustylnikov, Mariane B. Melo, Antu K. Dey","doi":"10.1038/s41541-024-00865-5","DOIUrl":"https://doi.org/10.1038/s41541-024-00865-5","url":null,"abstract":"<p>Varicella zoster virus (VZV) is a highly contagious human herpes virus responsible for causing chickenpox (varicella) and shingles (herpes zoster). Despite the approval of a highly effective vaccine, Shingrix^®, the global incidence of herpes zoster is increasing and the economic burden to the health care system and society are substantial due to significant loss of productivity and health complications, particularly among elderly and immunocompromised individuals. This is primarily because access to the vaccines remains mostly limited to countries within developed economies, such as USA and Canada. Therefore, similarly effective vaccines against VZV that are more accessible to the rest-of-the-world are necessary. In this study, we aimed to evaluate immunogenicity and memory response induced by three mRNA-LNP-based vaccine candidates targeting VZV’s surface glycoprotein E (gE). C57BL/6 mice were immunized with each candidate vaccine, and humoral and cellular immune responses were assessed. Our results demonstrate that the mRNA-LNP-based vaccine candidates elicited robust and durable humoral responses specific to the gE antigen. Notably, mice vaccinated with the mRNA-LNP vaccines exhibited significantly higher antigen-specific T-cell cytokine production compared to the group receiving Shingrix^®, the current standard of care vaccine. Additionally, mRNA-LNP vaccines induced long-lasting memory response, as evidenced by detection of persistent gE-specific Long-Lived Plasma Cells (LLPCs) and memory T cells four months after final immunization. These findings underscore the potential of our mRNA-LNP-based vaccine candidates in generating potent immune responses against VZV, offering promising prospects for their clinical development as an effective prophylactic vaccine against herpes zoster.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reverse development of vaccines against antimicrobial-resistant pathogens","authors":"Fabio Bagnoli, Ilaria Galgani, V. Kumaran Vadivelu, Sanjay Phogat","doi":"10.1038/s41541-024-00858-4","DOIUrl":"https://doi.org/10.1038/s41541-024-00858-4","url":null,"abstract":"<p>Vaccine R&amp;D is typically a lengthy process taking &gt;10 years. However, vaccines still fail in clinical development because of unreliable animal models or absent immunological correlates of protection. Without a correlate of protection, phase-1 and -2 studies of safety and immunogenicity can fail to predict phase-3 efficacy. Indeed, the history of vaccine development is replete with promising phase-1 and -2 results and failed phase-3 efficacy trials. To avoid this misfortune, we present <i>Reverse Vaccine Development</i> for vaccines against antimicrobial-resistant (AMR) pathogens. In this approach, instead of evaluating efficacy in phase 3, proof-of-principle efficacy is evaluated as early as possible in a population with a high incidence of disease, which may differ from the population intended for registration, and can be a controlled human infection population. To identify a correlate of protection in these populations, the vaccine-elicited immune response is compared between protected and unprotected subjects. If a correlate is identified, it can help to refine the vaccine dosage, schedule, and formulation, and facilitate the assessment of vaccine efficacy in other populations with different attack rates, subject characteristics, and disease manifestations. This may be the only way to provide life-saving vaccines to populations affected by AMR-pathogen diseases at incidences that are typically low and unsuited to phase-3 efficacy trials. The availability of a correlate of protection early in clinical development can potentially prevent failures of large phase-3 trials and unnecessary exposures of populations to inefficacious vaccines that have resulted in disinvestment in the development of vaccines against AMR pathogens.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140591313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress with COVID vaccine development and implementation.","authors":"Richard W Titball, David I Bernstein, Nicolas V J Fanget, Roy A Hall, Stephanie Longet, Paul A MacAry, Richard E Rupp, Marit van Gils, Veronika von Messling, David H Walker, Alan D T Barrett","doi":"10.1038/s41541-024-00867-3","DOIUrl":"10.1038/s41541-024-00867-3","url":null,"abstract":"","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10985065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptional signature of durable effector T cells elicited by a replication defective HCMV vaccine.","authors":"Xiaohua Ye, David J H Shih, Zhiqiang Ku, Junping Hong, Diane F Barrett, Richard E Rupp, Ningyan Zhang, Tong-Ming Fu, W Jim Zheng, Zhiqiang An","doi":"10.1038/s41541-024-00860-w","DOIUrl":"10.1038/s41541-024-00860-w","url":null,"abstract":"<p><p>Human cytomegalovirus (HCMV) is a leading infectious cause of birth defects and the most common opportunistic infection that causes life-threatening diseases post-transplantation; however, an effective vaccine remains elusive. V160 is a live-attenuated replication defective HCMV vaccine that showed a 42.4% efficacy against primary HCMV infection among seronegative women in a phase 2b clinical trial. Here, we integrated the multicolor flow cytometry, longitudinal T cell receptor (TCR) sequencing, and single-cell RNA/TCR sequencing approaches to characterize the magnitude, phenotype, and functional quality of human T cell responses to V160. We demonstrated that V160 de novo induces IE-1 and pp65 specific durable polyfunctional effector CD8 T cells that are comparable to those induced by natural HCMV infection. We identified a variety of V160-responsive T cell clones which exhibit distinctive \"transient\" and \"durable\" expansion kinetics, and revealed a transcriptional signature that marks durable CD8 T cells post-vaccination. Our study enhances the understanding of human T-cell immune responses to V160 vaccination.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984989/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140336319","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Highly stable and immunogenic CMV T cell vaccine candidate developed using a synthetic MVA platform.","authors":"Marcal Yll-Pico, Yoonsuh Park, Joy Martinez, Angelina Iniguez, Mindy Kha, Taehyun Kim, Leonard Medrano, Vu H Nguyen, Teodora Kaltcheva, Shannon Dempsey, Flavia Chiuppesi, Felix Wussow, Don J Diamond","doi":"10.1038/s41541-024-00859-3","DOIUrl":"10.1038/s41541-024-00859-3","url":null,"abstract":"<p><p>Human cytomegalovirus (CMV) is the most common infectious cause of complications post-transplantation, while a CMV vaccine for transplant recipients has yet to be licensed. Triplex, a multiantigen Modified Vaccinia Ankara (MVA)-vectored CMV vaccine candidate based on the immunodominant antigens phosphoprotein 65 (pp65) and immediate-early 1 and 2 (IE1/2), is in an advanced stage of clinical development. However, its limited genetic and expression stability restricts its potential for large-scale production. Using a recently developed fully synthetic MVA (sMVA) platform, we developed a new generation Triplex vaccine candidate, T10-F10, with different sequence modifications for enhanced vaccine stability. T10-F10 demonstrated genetic and expression stability during extensive virus passaging. In addition, we show that T10-F10 confers comparable immunogenicity to the original Triplex vaccine to elicit antigen-specific T cell responses in HLA-transgenic mice. These results demonstrate improvements in translational vaccine properties of an sMVA-based CMV vaccine candidate designed as a therapeutic treatment for transplant recipients.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10981716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140329960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials","authors":"Myra Happe, Amelia R. Hofstetter, Jing Wang, Galina V. Yamshchikov, LaSonji A. Holman, Laura Novik, Larisa Strom, Francis Kiweewa, Salim Wakabi, Monica Millard, Colleen F. Kelley, Sarah Kabbani, Srilatha Edupuganti, Allison Beck, Florence Kaltovich, Tamar Murray, Susanna Tsukerman, Derick Carr, Carl Ashman, Daphne A. Stanley, Aurélie Ploquin, Robert T. Bailer, Richard Schwartz, Fatim Cham, Allan Tindikahwa, Zonghui Hu, Ingelise J. Gordon, Nadine Rouphael, Katherine V. Houser, Emily E. Coates, Barney S. Graham, Richard A. Koup, John R. Mascola, Nancy J. Sullivan, Merlin L. Robb, Julie A. Ake, Kirsten E. Lyke, Mark J. Mulligan, Julie E. Ledgerwood, Hannah Kibuuka","doi":"10.1038/s41541-024-00833-z","DOIUrl":"https://doi.org/10.1038/s41541-024-00833-z","url":null,"abstract":"<p>Ebola virus disease (EVD) is a filoviral infection caused by virus species of the <i>Ebolavirus</i> genus including <i>Zaire ebolavirus</i> (EBOV) and <i>Sudan ebolavirus</i> (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored Ebola vaccine [either monovalent (cAd3-EBOZ) or bivalent (cAd3-EBO)] prime followed by a recombinant modified vaccinia virus Ankara EBOV vaccine (MVA-EbolaZ) boost in two phase 1/1b randomized open-label clinical trials in healthy adults in the United States (US) and Uganda (UG). Trial US (NCT02408913) enrolled 140 participants, including 26 EVD vaccine-naïve and 114 cAd3-Ebola-experienced participants (April-November 2015). Trial UG (NCT02354404) enrolled 90 participants, including 60 EVD vaccine-naïve and 30 DNA Ebola vaccine-experienced participants (February-April 2015). All tested vaccines and regimens were safe and well tolerated with no serious adverse events reported related to study products. Solicited local and systemic reactogenicity was mostly mild to moderate in severity. The heterologous prime-boost regimen was immunogenic, including induction of durable antibody responses which peaked as early as two weeks and persisted up to one year after each vaccination. Different prime-boost intervals impacted the magnitude of humoral and cellular immune responses. The results from these studies demonstrate promising implications for use of these vaccines in both prophylactic and outbreak settings.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":null,"pages":null},"PeriodicalIF":9.2,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140325517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}