NPJ VaccinesPub Date : 2025-06-11DOI: 10.1038/s41541-025-01175-0
Jason A Wojcechowskyj, Robyn M Jong, Imre Mäger, Britta Flach, Paul V Munson, Progya P Mukherjee, Barbara Mertins, Katherine R Barcay, Thomas Folliard
{"title":"Publisher Correction: Controlling reactogenicity while preserving immunogenicity from a self-amplifying RNA vaccine by modulating nucleocytoplasmic transport.","authors":"Jason A Wojcechowskyj, Robyn M Jong, Imre Mäger, Britta Flach, Paul V Munson, Progya P Mukherjee, Barbara Mertins, Katherine R Barcay, Thomas Folliard","doi":"10.1038/s41541-025-01175-0","DOIUrl":"10.1038/s41541-025-01175-0","url":null,"abstract":"","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"122"},"PeriodicalIF":6.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275485","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}
NPJ VaccinesPub Date : 2025-06-11DOI: 10.1038/s41541-025-01181-2
Gautam Sanyal
{"title":"Establishing correlation between in vitro potency and in vivo immunogenicity for mRNA vaccines.","authors":"Gautam Sanyal","doi":"10.1038/s41541-025-01181-2","DOIUrl":"10.1038/s41541-025-01181-2","url":null,"abstract":"<p><p>mRNA vaccines undergo intracellular translation to express the encoded protein antigen in a functionally intact form. To evaluate correlation between in vitro and in vivo measures of potency, mRNA vaccine samples with varying relative potencies can be created by gradual structural destabilization under stress including thermal stress. These samples can be tested in parallel for antigen expression in transfected cells and antigen-specific antibody induction and immune response in vaccinated animals.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"120"},"PeriodicalIF":6.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159153/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275482","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}
NPJ VaccinesPub Date : 2025-06-09DOI: 10.1038/s41541-025-01179-w
Thanh T N Phan, Devina J Thiono, Matthew G Hvasta, Ruby P Shah, Gisselle Prida Ajo, Wei-Chiao Huang, Jonathan F Lovell, Shaomin Tian, Aravinda M de Silva, Brian Kuhlman
{"title":"Multivalent administration of dengue E dimers on liposomes elicits type-specific neutralizing responses without immune interference.","authors":"Thanh T N Phan, Devina J Thiono, Matthew G Hvasta, Ruby P Shah, Gisselle Prida Ajo, Wei-Chiao Huang, Jonathan F Lovell, Shaomin Tian, Aravinda M de Silva, Brian Kuhlman","doi":"10.1038/s41541-025-01179-w","DOIUrl":"10.1038/s41541-025-01179-w","url":null,"abstract":"<p><p>The four serotypes of dengue virus (DENV1-4) are a major health concern putting 50% of the global population at risk of infection. Crucially, DENV vaccines must be tetravalent to provide protection against all four serotypes because immunity to only one serotype can enhance infections caused by heterologous serotypes. Uneven replication of live-attenuated viruses in tetravalent vaccines can lead to disease enhancement instead of protection. Subunit vaccines are a promising alternative as the vaccine components are not dependent on viral replication and antigen doses can be controlled to achieve a balanced response. Here, we show that a tetravalent subunit vaccine of dengue envelope (E) proteins computationally stabilized to form native-like dimers elicits type-specific neutralizing antibodies in mice against all four serotypes. The immune response was enhanced by displaying the E dimers on liposomes embedded with adjuvant, and no interference was detected between the four components.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"119"},"PeriodicalIF":6.9,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12149311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144258626","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}
NPJ VaccinesPub Date : 2025-06-07DOI: 10.1038/s41541-025-01173-2
Jin Gao, Galina Landgraf, Yue Yuan, Hai Yu, Soma Saeidi, Hyeog Kang, Mira Rakic Martinez, Luca Giurgea, Vladimir Lugovtsev, Jason Gorman, Matthew Memoli, Xi Chen, Zhiping Ye, Robert Daniels
{"title":"Influenza neuraminidase active site proximity assay for rapid profiling of inhibitory antibodies and antigenic drift.","authors":"Jin Gao, Galina Landgraf, Yue Yuan, Hai Yu, Soma Saeidi, Hyeog Kang, Mira Rakic Martinez, Luca Giurgea, Vladimir Lugovtsev, Jason Gorman, Matthew Memoli, Xi Chen, Zhiping Ye, Robert Daniels","doi":"10.1038/s41541-025-01173-2","DOIUrl":"10.1038/s41541-025-01173-2","url":null,"abstract":"<p><p>Efficient approaches that can help to select vaccine strains for the influenza virus neuraminidase (NA) antigen are currently needed to advance the development of vaccines containing NA. Here, we present a rapid and cost-effective solution-based NA active site proximity assay (NASPA) for measuring NA activity inhibitory (NAI) antibodies. This simplified assay uses large \"bulky\" NA active site-binding inhibitors to replace the sialylated glycoprotein substrates in common NA enzyme-linked lectin assay (ELLA) approaches. Our results with ferret antisera and monoclonal antibodies against vaccine strain NAs show a strong correlation between NASPA and ELLA titers, and that NASPA titers are not influenced by anti-HA antibodies. Consequently, NASPA can be used with influenza A or B strains and with the latter it revealed incremental antigenic changes in the NAs from recent B Victoria lineage vaccine strains. By coupling NASPA with a simple activity assay, we also found that steric and active site-binding NAI antibodies against circulating NAs are common in adult human sera. Finally, we demonstrate that NASPA can be modified by incorporating novel NA substrate-analog-based inhibitors. Together, these results suggest that NASPA can aid the development of vaccines containing NA by helping to select suitable vaccine strains and profile anti-NA antibody responses.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"118"},"PeriodicalIF":6.9,"publicationDate":"2025-06-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145422/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248942","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":"Next-gen novel nanocage-based multivalent vaccine candidate to tackle the rising menace of Mpox.","authors":"Rahul Ahuja, Preeti Vishwakarma, Varun Kumar, Ritika Khatri, Ananya Chatterjee, Surbhi Mishra, Zaigham Abbas Rizvi, Anup Singh, Gurleen Kaur, Vikas Maithil, Kunal Tarane, Akanksha Chauhan, Sarjeet Singh, Pooja Yadav, Devendra Yadav, Sangita Kumari Sinha, Syed Khalid Ali, Abhisek Chatterjee, Priyanka Priyadarsiny, Amit Awasthi, Vidya Mangala Prasad, Shubbir Ahmed, Sweety Samal","doi":"10.1038/s41541-025-01174-1","DOIUrl":"10.1038/s41541-025-01174-1","url":null,"abstract":"<p><p>The recent emergence and global spread of the human Monkeypox virus (MPXV), including its transmission to non-endemic regions, have raised significant global health concerns. In this proof-of-concept study, we developed a recombinant protein-based MPXV vaccine candidate, employing an innovative and versatile multivalent, self-assembled nanocage protein scaffold. Two immunogenic antigens derived from the contemporary circulating MPXV strain have been incorporated into a self-assembled non-structural protein-10 (NSP-10) scaffold, expressed, and purified using an Escherichia coli expression system without a purification tag. The vaccine candidate elicited strong antibody responses in mice and conferred protection against the lethal Vaccinia virus in an intranasal and skin pock in vivo study. Additionally, an intranasal challenge with the MPXV strain clade IIb in immunized mice demonstrated promising outcomes, including a significant reduction in viral titres and eliciting a robust neutralizing antibody response. This study demonstrates a feasible, scalable, and cost-effective approach for the development of the MPXV vaccine.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"117"},"PeriodicalIF":6.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12144111/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248943","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}
NPJ VaccinesPub Date : 2025-06-06DOI: 10.1038/s41541-025-01167-0
Elisa Fuentes, Chenjerai Jairoce, Didac Macià, Leonie Mayer, Jorge P Torres-Yaguana, Marta Vidal, Rebeca Santano, David L Narum, David Cavanagh, Benoit Gamain, Ross L Coppel, James G Beeson, Sheetij Dutta, Jahit Sacarlal, Ruth Aguilar, Gemma Moncunill, Carlota Dobaño
{"title":"Role of malaria exposure and off-target responses on RTS,S/AS02<sub>A</sub> vaccine immunogenicity and protection in Mozambican children.","authors":"Elisa Fuentes, Chenjerai Jairoce, Didac Macià, Leonie Mayer, Jorge P Torres-Yaguana, Marta Vidal, Rebeca Santano, David L Narum, David Cavanagh, Benoit Gamain, Ross L Coppel, James G Beeson, Sheetij Dutta, Jahit Sacarlal, Ruth Aguilar, Gemma Moncunill, Carlota Dobaño","doi":"10.1038/s41541-025-01167-0","DOIUrl":"10.1038/s41541-025-01167-0","url":null,"abstract":"<p><p>RTS,S/AS01<sub>E</sub> is the first malaria vaccine implemented for young African children. However, it provides partial protection against Plasmodium falciparum (Pf) malaria, and a better understanding of the mechanisms and determinants of vaccine immunity will help develop second-generation improved vaccines. We measured IgG to vaccine target and Pf blood-stage off-target proteins before and after vaccination in 874 children aged 1-4 years in a phase 2b trial of RTS,S/AS02<sub>A</sub> in Mozambique. We found that naturally acquired PfCSP IgG levels pre-vaccination were positively associated with RTS,S immunogenicity. Increased levels of IgG to the C-terminus and NANP-repeat regions of PfCSP, and to PfMSP5 and PfMSP1 block 2, following vaccination, were significantly associated with a lower hazard of clinical malaria over 6 months. Thus, immune priming, anti-PfCSP C-terminus and off-target antibody responses contributed to malaria protection after adjusting for prior Pf exposure, and this could guide strategies for optimizing the immunogen and vaccine deployment.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"116"},"PeriodicalIF":6.9,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141681/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234666","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}
NPJ VaccinesPub Date : 2025-06-05DOI: 10.1038/s41541-025-01178-x
Dongrong Yi, Qian Liu, Saisai Guo, Quanjie Li, Yongxin Zhang, Ning Li, Qili Zhang, Kai Lv, Ni An, Lu Han, Hua Chen, Yi Wang, Chunyan Chang, Huihan Shao, Jing Wang, Xiaoyu Li, Linlin Bao, Dayan Wang, Guoyang Liao, Chunjian Huang, Weiguo Zhang, Yijie Dong, Yuelong Shu, Shan Cen
{"title":"Chimeric hemagglutinin and M2 mRNA vaccine for broad influenza subtype protection.","authors":"Dongrong Yi, Qian Liu, Saisai Guo, Quanjie Li, Yongxin Zhang, Ning Li, Qili Zhang, Kai Lv, Ni An, Lu Han, Hua Chen, Yi Wang, Chunyan Chang, Huihan Shao, Jing Wang, Xiaoyu Li, Linlin Bao, Dayan Wang, Guoyang Liao, Chunjian Huang, Weiguo Zhang, Yijie Dong, Yuelong Shu, Shan Cen","doi":"10.1038/s41541-025-01178-x","DOIUrl":"10.1038/s41541-025-01178-x","url":null,"abstract":"<p><p>Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics, developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy, we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs, as well as highly pathogenic avian influenza. Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies, T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries. In particular, intramuscular administration stimulated systemic immunity together with a prominent lung tropism of memory cells. Moreover, Fluaxe immunization inhibited the inflammatory response induced by influenza infection. In summary, we conclude that Fluaxe can elicit broad cross-protection against numerous influenza subtypes.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"113"},"PeriodicalIF":6.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141470/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234664","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":"Characterization of a suspension Vero cell line for viral vaccine production.","authors":"Léa Bourigault, Corinne Bresson, Christian Jean, Christophe Chevalard, Mathilde Kloutz, Damien Soulet, Fleurine Pelissier, Stéphanie Richard, Isabelle Bassard, Nicolas Sève, Cédric Charretier, Bertrand Pain","doi":"10.1038/s41541-025-01157-2","DOIUrl":"10.1038/s41541-025-01157-2","url":null,"abstract":"<p><p>Vero cells, as approved by the World Health Organization, have been the most commonly used continuous cell line for viral vaccine production over the last 25 years, but their adherent phenotype continues to limit productivity. Adapting to a suspension culture would overcome this restriction and reduce production costs. First, a Vero suspension isolate was obtained and metabolically characterized. Second, RNA sequencing analysis was used to identify differentially expressed genes between adherent and suspension cells, which revealed complete downregulation of adhesion and matrix-associated genes. Additionally, signaling pathways involving Wnt and other tyrosine kinase receptors were identified as potential leads for growth optimization. In particular, supplementation with fibroblast growth factor 2 allowed for a 20% increase in cell density. Finally, a comparative viral productivity assay revealed a 30% increase in poliovirus production in suspension Vero cells compared to adherent cells depending on the serotype, as well as a 140% increase in respiratory syncytial virus production and a 150% increase in yellow fever virus production. This work establishes the potential of the suspension Vero cell line as a new cell platform for viral vaccine production.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"114"},"PeriodicalIF":6.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234663","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}
NPJ VaccinesPub Date : 2025-06-05DOI: 10.1038/s41541-025-01180-3
M Visser, D M van Rooijen, J Wolf, L Beckers, M Ohm, M I de Jonge, A M Buisman, G den Hartog
{"title":"Immunogenicity of primary and booster MenACWY-TT vaccination in older adults and the importance of IgM.","authors":"M Visser, D M van Rooijen, J Wolf, L Beckers, M Ohm, M I de Jonge, A M Buisman, G den Hartog","doi":"10.1038/s41541-025-01180-3","DOIUrl":"10.1038/s41541-025-01180-3","url":null,"abstract":"<p><p>Adults aged 65 years and older are at increased risk for infectious diseases, including invasive meningococcal disease (IMD), yet data on meningococcal vaccine immunogenicity in this population remain limited. In this randomized clinical trial (CTIS: 2024-513640-29-00, 13-05-2024), 222 older adults (65-85 years) received a quadrivalent meningococcal conjugate vaccine (MenACWY-TT), with 104 adults receiving a booster dose one year later. Serum bactericidal activity (rSBA) and polysaccharide-specific IgG and IgM concentrations were assessed. One month post-primary vaccination, 91-98% of participants had protective rSBA titers (≥8). Booster vaccination transiently increased bactericidal responses, but titers returned to pre-booster values within a year for MenC, -W, and -Y. rSBA titers correlated stronger with IgM than IgG, particularly for MenW and -Y. Interestingly, IgM depletion markedly reduced rSBA titers, while IgG depletion had minimal impact. These findings highlight that MenACWY-TT vaccination elicits functional antibody responses in older adults, largely driven by IgM.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"115"},"PeriodicalIF":6.9,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12141617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234665","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}
NPJ VaccinesPub Date : 2025-06-03DOI: 10.1038/s41541-025-01166-1
Abhinay Gontu, Sougat Misra, Shubhada K Chothe, Santhamani Ramasamy, Padmaja Jakka, Maurice Byukusenge, Lindsey C LaBella, Meera Surendran Nair, Bhushan M Jayarao, Marco Archetti, Ruth H Nissly, Suresh V Kuchipudi
{"title":"Trans amplifying mRNA vaccine expressing consensus spike elicits broad neutralization of SARS CoV 2 variants.","authors":"Abhinay Gontu, Sougat Misra, Shubhada K Chothe, Santhamani Ramasamy, Padmaja Jakka, Maurice Byukusenge, Lindsey C LaBella, Meera Surendran Nair, Bhushan M Jayarao, Marco Archetti, Ruth H Nissly, Suresh V Kuchipudi","doi":"10.1038/s41541-025-01166-1","DOIUrl":"10.1038/s41541-025-01166-1","url":null,"abstract":"<p><p>SARS-CoV-2 continues to evolve and evade vaccine immunity necessitating vaccines that offer broad protection across variants. Conventional mRNA vaccines face cost and scalability challenges, prompting the exploration of alternative platforms like trans-amplifying (TA) mRNA that offer advantages in safety, manufacturability, and antigen dose optimization. Using consensus sequence of immunodominant antigens is a promising antigen design strategy for board cross-protection. Combining these two features, we designed and evaluated a TA mRNA vaccine encoding a consensus spike protein from SARS-CoV-2. Mice receiving the TA mRNA vaccine produced neutralizing antibody levels comparable to a conventional mRNA vaccine using 40 times less antigen mRNA. In hACE2 transgenic mice challenged with the Omicron BA.1 variant, the TA mRNA vaccine reduced lung viral titers by over 10-fold and induced broadly cross-neutralizing antibodies against multiple variants. These findings highlight the potential of TA mRNA vaccines with consensus antigen design, to improve efficacy and adaptability against SARS-CoV-2 variants.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"110"},"PeriodicalIF":6.9,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12134344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144216418","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}
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