NPJ Vaccines最新文献

{"title":"Virus-like particle vaccines targeting a key epitope in circumsporozoite protein provide sterilizing immunity against malaria.","authors":"Yogesh Nepal, Alexandra Francian, Yevel Flores-Garcia, Bryce T Roberts, Sunil A David, Fidel Zavala, Bryce Chackerian","doi":"10.1038/s41541-025-01241-7","DOIUrl":"10.1038/s41541-025-01241-7","url":null,"abstract":"<p><p>Vaccines that target the pre-erythrocytic stage of the malaria lifecycle have the potential to provide sterilizing immunity but must elicit sustained, high-titer antibody responses to completely prevent infection. Most pre-erythrocytic vaccines target circumsporozoite protein (CSP), the major surface antigen on Plasmodium falciparum sporozoites. Antibodies targeting distinct epitopes within the central repeat region of CSP have the potential to provide protection from infection, but we have focused on developing vaccines that target a highly vulnerable CSP epitope that is targeted by the potent monoclonal antibody L9. In a previous study, we produced a pre-erythrocytic vaccine displaying a synthetic peptide representing the L9 epitope on Qβ bacteriophage virus-like particles (VLPs). This vaccine elicited strong anti-CSP antibody responses that protected mice from malaria challenge. Here, we asked whether the structural context of the L9 epitope influences the quality of antibody responses. We compared the immunogenicity and protective efficacy of Qβ L9 VLPs to recombinant VLPs that display the L9 peptide in a structure that is hypothesized to mimic its native conformation. Recombinant MS2 bacteriophage VLPs displaying various lengths of the L9 epitope were produced and immunogenicity and protective efficacy were evaluated in mice. Our results demonstrate that MS2 L9 VLPs, particularly those displaying longer L9 peptides and in combination with a potent novel adjuvant, elicit strong and durable antibody responses that lower malaria liver burden and prevent infection. We also compared the efficacy of L9-targeted vaccines to the licensed vaccine, RTS,S/AS01_E (Mosquirix™, GSK). Immunization with Qβ L9 VLPs, MS2 L9 VLPs, and RTS,S/AS01_E provided significant protection from liver-stage infection in a mouse model. Interestingly, immunization with a combination vaccine consisting of MS2 L9 and Qβ L9 VLPs, each presenting the L9 epitope in a distinct structural context, elicited sterilizing immunity in the highest percentage of mice.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"176"},"PeriodicalIF":6.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12311073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753905","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":"De-risking vaccine development: lessons, challenges, and prospects.","authors":"Vega Masignani, Ricardo Palacios, Marie-Thérèse Martin, Fabian Tibaldi, V Kumaran Vadivelu","doi":"10.1038/s41541-025-01211-z","DOIUrl":"10.1038/s41541-025-01211-z","url":null,"abstract":"<p><p>Vaccine development is long and costly. Technical, clinical, regulatory, and manufacturing risks throughout the development cycle hampered manufacturers' efforts towards more challenging and financially less rewarding targets, with profound implications for public health. Early de-risking strategies can help closing the vaccine productivity gap and support sustainable access to vaccines. Illustrated by examples of early and efficient decision-making, the herein proposed strategies can ultimately increase the success rates of vaccine programs.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"177"},"PeriodicalIF":6.5,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12310957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144753904","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":"Diversity of immunization strongly impacts SARS-CoV-2 antibody function surrogates.","authors":"Benoît Levast, Jérémie Becker, Carla Saade, Inès VuDuc, Kendra Reynaud, Camilo Broc, Charlotte Mignon, Natacha Mariano, Stéphanie Donnat, Shin-Yi Yu, Adrien Saliou, Viet-Dung Tran, Oxana Vratskikh, Céline Couturier, Stéphanie Geoffroy, Anely Tranchot, Christophe Vedrine, Tom Perisse, Lily Bruyere, Martin Killian, Bruno Pozzetto, Karen Louis, Laurent Beloeil, Cyril Guyard, Stéphane Paul, Arnaud Marchant, Sophie Trouillet-Assant","doi":"10.1038/s41541-025-01226-6","DOIUrl":"10.1038/s41541-025-01226-6","url":null,"abstract":"<p><p>System serology offers a comprehensive approach to evaluate the humoral immune response by evaluating multiple parameters. In the present study, based on four groups of individuals with a different history of SARS-CoV-2 immunization, we analyzed the serum of 180 individuals based on six serological methods to better decipher their immunity. Through our analysis, against different SARS-CoV-2 antigens or variants, we report the importance of system serology to better decipher population immunity. Fc-dependent parameters are key factors underlying the variability of humoral immune response triggered by different schemes of SARS-CoV-2 immunization. With an evolving exposure to new variants, the acquisition of robust cross-reactive Fc-dependent effector functions are likely to be key to control viral replication when neutralizing antibodies are poorly cross-reactive. As booster vaccination remains a useful tool in periodically bolstering humoral immunity, particularly in vulnerable populations, studies should continue to evaluate the humoral immune response using system serology approach.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"175"},"PeriodicalIF":6.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144743355","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":"A novel nanoparticle vaccine displaying multistage tuberculosis antigens confers protection in mice infected with H37Rv.","authors":"Yanbin Ding, Yuanyuan Li, Zhuhua Wu, Yu Zhou, Yan Guo, Siyu Tian, Rui Yu, Chunping Deng, Rui Wei, Hang Chen, Yan Li, Xiaokang Zhang, Wenjia Yu, Cai Jing, Shuyun Liu, Lili Qin, Meng Lyu, Yongjuan Zou, Yuanfeng Yao, Lu Tan, Shifen Wu, Weilong Liu, Xunxun Chen, Jing Jin","doi":"10.1038/s41541-025-01216-8","DOIUrl":"10.1038/s41541-025-01216-8","url":null,"abstract":"<p><p>Tuberculosis remains a major global health threat, as Bacillus Calmette-Guérin (BCG), the only licensed vaccine, provides limited protection, particularly in adolescents and adults. To address this limitation, a more effective tuberculosis vaccine was developed using the SpyTag/SpyCatcher system to display five clinically validated Mycobacterium tuberculosis antigens (Ag85A, ESAT-6, CFP10, Rv2660c, and TB10.4) on self-assembling mi3 nanoparticles. These nanoparticle-displayed antigens, formulated as 85A-NP, EC-NP, and RT-NP and combined with a custom AS01E-biosimilar adjuvant, elicited stronger Th1-biased immune responses in C57BL/6 mice than the corresponding recombinant proteins, as evidenced by increased frequencies of polyfunctional CD4⁺ T cells producing IFN-γ, IL-2, and TNF-α. In a murine aerosol challenge model, the mixed nanoparticles formulation (85A-NP:EC-NP:RT-NP) conferred superior pulmonary protection compared to single-antigen nanoparticles, recombinant protein mixtures, an in-house M72-like vaccine and BCG. This modular platform enables efficient multistage antigen incorporation and holds promise for next-generation tuberculosis vaccine development.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"173"},"PeriodicalIF":6.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144743354","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":"A Bayesian network analysis of the Pfizer COVID-19 vaccine in the paediatric population.","authors":"Tej Shukla, Helen J Mayfield, John C B Litt, Samuel J Brown, Jane Sinclair, Sophie Wen, Philip N Britton, Rajesh Puranik, Kirsty R Short, Tina Moghaddam, Olivia Williams, Colleen L Lau, Amalie Dyda","doi":"10.1038/s41541-025-01237-3","DOIUrl":"10.1038/s41541-025-01237-3","url":null,"abstract":"<p><p>The Pfizer COVID-19 vaccines have been associated with an increased risk of myocarditis. However, COVID-19 infection is also associated with complications. A Bayesian network (BN), informed by Australian and international data, was created to determine individual risks and benefits of the Pfizer COVID-19 vaccine in the paediatric. The risk of myocarditis between vaccine-associated, COVID-19 and background rates was compared, as well as secondary outcomes such as hospitalization, and MIS-C. At a population level, hospitalizations, intensive care admissions and MIS-C cases prevented at differing transmission rates and vaccine coverage were analyzed. The model estimated that teenage males were 4.47 times more likely to develop myocarditis from COVID-19 compared to the vaccine. Furthermore, the risk of hospitalizations and MIS-C were more likely in the unvaccinated cohort for all ages. The population level benefits of COVID-19 Pfizer vaccine at mitigating myocarditis are more nuanced, contingent on age, transmission rates and vaccination coverage.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"174"},"PeriodicalIF":6.5,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12307593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144743353","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":"Cost-effectiveness of chikungunya vaccination with the live attenuated vaccine in U.S. territories.","authors":"Kelly Kilburn, Martin I Meltzer, Seonghye Jeon, Bishwa B Adhikari, Nicole Lindsey, Susan L Hills, J Erin Staples","doi":"10.1038/s41541-025-01194-x","DOIUrl":"10.1038/s41541-025-01194-x","url":null,"abstract":"<p><p>A live attenuated chikungunya vaccine, IXCHIQ, was approved in the United States in 2023 for use in adults. We assessed the cost-effectiveness of two different vaccination strategies, routine and outbreak vaccination, for persons aged ≥18 years living in U.S. territories with previous transmission. We included the entire population of impacted U.S. territories and assumed one chikungunya outbreak occurring during a 30-year time horizon. We estimated that routine vaccination would avert 90% of the disease burden and cost $498 million (16% savings compared with no vaccination) while outbreak vaccination would avert 67% of the disease burden and cost $552 million (6% savings). Both strategies were more costly than no vaccination from the healthcare payer perspective. Routine vaccination was cost-saving for all outcomes assessed from a societal perspective. Outbreak vaccination was cost-saving for averted symptomatic cases but cost from $5 [95% CI: cost savings, $191] per chronic joint pain case averted to $373,054 [95% CI: $172,643, $573,464] per death averted.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"172"},"PeriodicalIF":6.5,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12304215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732429","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":"Malaria bivalent viral vectored vaccine protects against Plasmodium falciparum and vivax and blocks parasite transmission.","authors":"Yutaro Yamamoto, Takuto Katayama, Camila Fabbri, Sora Niwa, Daiki Okuhara, Mitsuhiro Iyori, Ammar A Hasyim, Hiroaki Mizukami, Hisatoshi Shida, Stefanie Lopes, Shigeto Yoshida","doi":"10.1038/s41541-025-01229-3","DOIUrl":"10.1038/s41541-025-01229-3","url":null,"abstract":"<p><p>Malaria remains a major infectious disease, with Plasmodium falciparum and Plasmodium vivax often co-endemic, requiring a dual-target vaccine for adequate control. We previously developed monovalent vaccines against P. falciparum or P. vivax using vaccinia virus LC16m8Δ (m8Δ) and adeno-associated virus type 1 (AAV1). Here, we demonstrate the efficacy of a novel bivalent malaria vaccine against P. falciparum and P. vivax. The m8Δ vaccine harbors two gene cassettes encoding Pfs25-PfCSP and Pvs25-PvCSP fusion proteins, while the AAV1 vaccine includes two recombinant AAV1s carrying one of these cassettes as a mixture. Heterologous m8Δ-prime and AAV1-boost immunization provided 70% protection against both PfCSP/Pb and PvCSP/Pb transgenic sporozoites. Moreover, a membrane feeding assay using P. vivax isolates from infected patients in the Brazilian Amazon showed 90% transmission-blocking efficacy. The bivalent vaccine outperformed monovalent combinations, maintaining immune responses for over 7 months, and shows promise for malaria control and elimination.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"171"},"PeriodicalIF":6.5,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718177","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":"Development of a bivalent protein subunit vaccine against infection by Pseudomonas aeruginosa and Staphylococcus aureus.","authors":"Suhrid Maiti, Prolay Halder, Debaki Ranjan Howlader, Zackary K Dietz, Satabdi Biswas, Md Shafiullah Parvej, Mst Nusrat Zahan, Ti Lu, Timothy A Snider, Sean K Whittier, William D Picking, Wendy L Picking","doi":"10.1038/s41541-025-01220-y","DOIUrl":"10.1038/s41541-025-01220-y","url":null,"abstract":"<p><p>Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) are members of the ESKAPE pathogens, a group of bacteria that are a threat to human health due to their ability to resist antibiotics. They are known to cause severe infections, often as co-morbidities, in individuals with conditions such as people with cystic fibrosis, diabetes, wounds, pneumonia, and critically ill patients requiring intubation leading to ventilator-associated pneumonia. Emergence of multi-drug resistance in SA and PA is making traditional antibiotic treatment ineffective and unfortunately there are no licensed vaccines to prevent MRSA or PA infections. We have demonstrated that when delivered intranasally (IN) L-PaF, a genetic fusion of the PA type III secretion system (T3SS) proteins PcrV and PopB (PaF) with LTA1, the active moiety of heat-labile enterotoxin from enterotoxigenic E. coli, protects against PA. L-PaF was formulated as a nanoemulsion (ME) to increase the protective immune response against clinically relevant PA strains in a mouse lung colonization model. With the addition NEAT2, the heme capturing domain of the SA protein IsdB, a bivalent vaccine was generated. IN administration of the bivalent formulation protected MRSA pre-exposed mice from both MRSA and PA infection. Sera from mice vaccinated with our formulation contained strong IgG titers with high levels of opsonophagocytic killing of homologous and heterologous PA and SA strains. Additionally, the bivalent L-PaF/NEAT2 formulation elicited stimulation of IL-17A and IL-2 cytokines. Because established PA and SA lung infection models with rabbits better reproduce the clinical hallmarks of severe human acute pneumonia, rabbits were immunized with the bivalent L-PaF/NEAT2 formulation. All of the vaccinated rabbits survived the challenges while the controls did not. These findings demonstrate that our L-PaF/ME/NEAT2 formulation has potential as a broad-spectrum vaccine against both SA and PA infection.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"169"},"PeriodicalIF":6.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297384/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718176","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":"Maternal vaccination with live-attenuated Rift Valley fever virus protects offspring via immune transfer.","authors":"Austin T Hertel, Cynthia M McMillen, Ryan M Hoehl, Dominique J Barbeau, Anita K McElroy, Amy L Hartman","doi":"10.1038/s41541-025-01230-w","DOIUrl":"10.1038/s41541-025-01230-w","url":null,"abstract":"<p><p>Rift Valley fever virus (RVFV) causes high rates of spontaneous abortions and neonatal mortality in ruminants resulting in severe socioeconomic and public health consequences. Maternal vaccination may protect pregnant animals, fetuses, and neonates via transfer of maternal antibodies; however, currently available live-attenuated RVFV vaccines are generally unsafe for use during pregnancy. RVFV-delNSs/NSm is a live attenuated strain that has demonstrated favorable safety and efficacy in pregnant livestock, yet studies investigating maternal vaccination as a strategy to protect neonates from RVF are limited. Using pregnant Sprague-Dawley rats, we show that maternal vaccination with RVFV-delNSs/NSm leads to efficient transfer of anti-RVFV antibodies to offspring. These offspring were completely protected from lethal RVFV challenge. Although further investigation is required in susceptible ruminant species, our findings indicate that maternal anti-RVFV immunity is sufficient to protect offspring, highlighting maternal vaccination as a potential strategy to reduce RVF disease burden in endemic regions.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"168"},"PeriodicalIF":6.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297433/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718178","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":"Targeting Langerhans cells via skin delivery of HIV Envelope enhances the antibody response to vaccination.","authors":"Juliane S Lanza, Adele Hammoudi, Joanna De Chiara, Mathieu Surenaud, Anaïs Kembou, Michela Esposito, Sandra Zurawski, Gerard Zurawski, Mireille Centlivre, Bernard Malissen, Véronique Godot, Yves Lévy, Sandrine Henri, Sylvain Cardinaud","doi":"10.1038/s41541-025-01214-w","DOIUrl":"10.1038/s41541-025-01214-w","url":null,"abstract":"<p><p>Targeting dendritic cells (DCs) with antigens is a promising approach to modulating T follicular helper (Tfh) cells and germinal center (GC) reactions, enhancing vaccine-induced adaptive immune responses, with preclinical studies highlighting a key role of Langerhans cells (LCs) in generating HIV-1-specific antibody responses. This study evaluated the immunogenicity of a Langerin-targeting vaccine (αLang.Env), comprising an anti-mouse Langerin mAb fused to HIV-1 Envelope 96ZM651 gp140 (Env), delivered through various skin immunization routes in mice, and explored the roles of epidermal LCs and dermal cDC1s in adaptive immune responses. Lymph nodes draining the immunization sites were analyzed using ovalbumin (OVA) as a surrogate antigen after topical (top.), subcutaneous (s.c.), intradermal (i.d.), or transcutaneous (t.c.) delivery via laser-guided microporation, with αLang.Env administered without adjuvant in a Prime-Boost scheme. All methods primed T cells in draining lymph nodes (dLN), as shown by OVA-specific CD8⁺ and CD4⁺ T cell proliferation, while αLang.Env induced GC B cells regardless of the route. However, topical delivery did not elicit Tfh cells or Env-specific GC B cells, whereas i.d. and s.c. routes produced systemic Env-specific IgG responses, with i.d. immunization yielding the highest titers and strongest Tfh responses. In the Xcr1^DTA mouse model, where cDC1s were depleted, the i.d. route confirmed that epidermal LCs were the primary drivers of GC/Tfh reactions and humoral responses, while cDC1s mediated CD8⁺ T cell effector responses. These findings highlight that i.d. administration of the HIV-1 Env antigen targeted to Langerin, without the use of an adjuvant, is an effective vaccine strategy for eliciting GC reactions in LN and generating robust antibody responses, primarily through the activation of LC.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"170"},"PeriodicalIF":6.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297313/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718179","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}