NPJ VaccinesPub Date : 2025-03-28DOI: 10.1038/s41541-025-01110-3
María-José Felgueres, Gloria Esteso, Álvaro F García-Jiménez, Alberto Benguría, Enrique Vázquez, Nacho Aguiló, Eugenia Puentes, Ana Dopazo, Ingrid Murillo, Carlos Martín, Esteban Rodríguez, Hugh T Reyburn, Mar Valés-Gómez
{"title":"Cytolytic γδ T-cells and IFNγ-producing CD4-lymphocytes characterise the early response to MTBVAC tuberculosis vaccine.","authors":"María-José Felgueres, Gloria Esteso, Álvaro F García-Jiménez, Alberto Benguría, Enrique Vázquez, Nacho Aguiló, Eugenia Puentes, Ana Dopazo, Ingrid Murillo, Carlos Martín, Esteban Rodríguez, Hugh T Reyburn, Mar Valés-Gómez","doi":"10.1038/s41541-025-01110-3","DOIUrl":"10.1038/s41541-025-01110-3","url":null,"abstract":"<p><p>Infection with Mycobacterium tuberculosis (Mtb) can produce a wide spectrum of clinical manifestations, ranging from active tuberculosis (TB) to asymptomatic latent infection. Although CD4 T-cells are key immune effectors to control TB, early after infection, the innate immune response must play a role in tackling the disease. Here, we performed in-depth analyses of the acute immune response to MTBVAC, a candidate vaccine engineered from Mtb with the aim of protecting adults from pulmonary TB disease, still a major global challenge. scRNA-seq shows expansion of CD4<sup>+</sup> and cytotoxic γδ T-cells, data confirmed by flow cytometry. CD4 T-cells exhibited lower HLA-DR and higher L-selectin expression, compared to BCG-stimulation, indicating differential activation or dynamics. Importantly, MTBVAC-activated γδ T-cells had a unique cytotoxic CD16<sup>+</sup>GZMB<sup>+</sup> phenotype, reminiscent of effector cells found in Mtb positive individuals controlling infection. IFN-γ and TNF-α were released in cultures, while IL-17A/F were almost undetectable.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"58"},"PeriodicalIF":6.9,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11953372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143743282","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 : 2025-03-26DOI: 10.1038/s41541-025-01116-x
Jacent Nassuuna, Joas Sterk, Bridgious Walusimbi, Agnes Natukunda, Ronald Nkangi, Rebecca Amongin, Ludoviko Zirimenya, Emily L Webb, Alison M Elliott, Gyaviira Nkurunungi
{"title":"Helminth driven gut inflammation and microbial translocation associate with altered vaccine responses in rural Uganda.","authors":"Jacent Nassuuna, Joas Sterk, Bridgious Walusimbi, Agnes Natukunda, Ronald Nkangi, Rebecca Amongin, Ludoviko Zirimenya, Emily L Webb, Alison M Elliott, Gyaviira Nkurunungi","doi":"10.1038/s41541-025-01116-x","DOIUrl":"10.1038/s41541-025-01116-x","url":null,"abstract":"<p><p>Vaccine responses are sometimes impaired in rural, low-income settings. Helminth-associated gut barrier dysfunction and microbial translocation (MT) may be implicated. We used samples from a trial of praziquantel treatment-effects on vaccine responses in Schistosoma mansoni (Sm)-endemic Ugandan islands, measuring intestinal fatty acid-binding protein 2 (I-FABP2), lipopolysaccharide-binding protein, anti-endotoxin core antibodies (EndoCab), soluble CD14 (sCD14) in plasma, and faecal lipocalin-2, occult blood (FOB), and calprotectin (fCAL), and evaluating their associations with baseline helminth infection, praziquantel treatment, and responses to BCG, yellow fever, typhoid, HPV, and tetanus-diphtheria vaccines. Sm associated positively with fCAL and FOB, hookworm with I-FABP2, and any helminth with EndoCab IgM, fCAL and FOB. Sm associated inversely with sCD14. Praziquantel treatment reduced all marker concentrations, significantly fCAL and FOB, implying that Sm-associated gut inflammation and MT is reversible. Associations of assessed markers with vaccine-specific responses were predominantly inverse. Interventions to improve gut barrier function may enhance vaccine responsiveness.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"56"},"PeriodicalIF":6.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143720955","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 : 2025-03-22DOI: 10.1038/s41541-025-01106-z
Jinpan Hu, Zijing Jia, Meng Wang, Lingling Nie, Wangjun Fu, Qingfeng Zhang, Haiyang Qin, Jianhui Nie, Xiaoyu Xu, Lingjie Xu, Fengze Wang, Yingping Chen, Bo Xing, Tao Li, Danfeng Li, Shaowei Li, Ningshao Xia, Xiangxi Wang, Weijin Huang
{"title":"Establishing a universal IVRP method for quadrivalent HPV vaccines to replace in vivo potency tests.","authors":"Jinpan Hu, Zijing Jia, Meng Wang, Lingling Nie, Wangjun Fu, Qingfeng Zhang, Haiyang Qin, Jianhui Nie, Xiaoyu Xu, Lingjie Xu, Fengze Wang, Yingping Chen, Bo Xing, Tao Li, Danfeng Li, Shaowei Li, Ningshao Xia, Xiangxi Wang, Weijin Huang","doi":"10.1038/s41541-025-01106-z","DOIUrl":"10.1038/s41541-025-01106-z","url":null,"abstract":"<p><p>Several human papillomavirus (HPV) L1-based virus-like particle (VLP) vaccines are in development to meet future global vaccination needs. Type-specific monoclonal antibodies with good reactivity to all types of vaccines are urgently needed to evaluate vaccine potency. In this study, binding activity, neutralizing activity, conformational sensitivity, immunodominance in human serum, and versatility were compared among antibodies. A broad-spectrum binding antibody (C4-F5-127) was selected as the capture antibody; four type-specific neutralizing antibodies (6-F5-77, 11-F5-187, 16-F5-196, and 18-F5-203) were selected as detection antibodies for HPV6, 11, 16, and 18, respectively. These antibodies formed a standardized and universal in vitro relative potency (IVRP) assay kit. High-resolution cryo-electron microscopy (cryo-EM) structures of HPV6-6-F5-77, HPV11-11-F5-187, HPV16-16-F5-196 and HPV18-18-F5-203 complexes define the location and nature of epitopes, revealing serotype specific binding modes and neutralization mechanisms. The IVRP results were correlated with potency data from mouse models, offering an efficient alternative to in vivo potency experiments.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"55"},"PeriodicalIF":6.9,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928608/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677026","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 : 2025-03-20DOI: 10.1038/s41541-025-01107-y
Christian Garde, Michail A Pavlidis, Pablo Garces, Emma J Lange, Sri H Ramarathinam, Mateo Sokač, Kirti Pandey, Pouya Faridi, Johanne Ahrenfeldt, Shanzou Chung, Stine Friis, Daniela Kleine-Kohlbrecher, Nicolai J Birkbak, Jens V Kringelum, Birgitte Rønø, Anthony W Purcell, Thomas Trolle
{"title":"Endogenous viral elements constitute a complementary source of antigens for personalized cancer vaccines.","authors":"Christian Garde, Michail A Pavlidis, Pablo Garces, Emma J Lange, Sri H Ramarathinam, Mateo Sokač, Kirti Pandey, Pouya Faridi, Johanne Ahrenfeldt, Shanzou Chung, Stine Friis, Daniela Kleine-Kohlbrecher, Nicolai J Birkbak, Jens V Kringelum, Birgitte Rønø, Anthony W Purcell, Thomas Trolle","doi":"10.1038/s41541-025-01107-y","DOIUrl":"10.1038/s41541-025-01107-y","url":null,"abstract":"<p><p>Personalized cancer vaccines (PCVs) largely leverage neoantigens arising from somatic mutations, limiting their application to patients with relatively high tumor mutational burden (TMB). This underscores the need for alternative antigens to design PCVs for low TMB cancers. To this end, we substantiate endogenous retroviral elements (EVEs) as tumor antigens through large-scale genomic analyses of healthy tissues and solid cancers. These analyses revealed that the breadth of EVE expression in tumors stratify checkpoint inhibitor-treated melanoma patients into groups with differential overall and progression-free survival. To enable the design of PCVs containing EVE-derived epitopes with therapeutic potential, we developed a computational pipeline, ObsERV. We show that EVE-derived peptides are presented as epitopes on tumors and can be predicted by ObsERV. Preclinical testing of ObsERV demonstrates induction of sustained poly-functional CD4+ and CD8+ T-cell responses as well as long-term tumor protection. As such, EVEs may facilitate and improve PCVs, especially for low-TMB patients.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"54"},"PeriodicalIF":6.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11926357/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670321","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 : 2025-03-20DOI: 10.1038/s41541-025-01072-6
Elizabeth P Schlaudecker, Travis L Jensen, Casey E Gelber, Phillip J Dexheimer, Mark C Steinhoff, David I Bernstein, Johannes B Goll
{"title":"Transcriptome analysis in human breast milk and blood in a randomized trial after inactivated or attenuated influenza immunization.","authors":"Elizabeth P Schlaudecker, Travis L Jensen, Casey E Gelber, Phillip J Dexheimer, Mark C Steinhoff, David I Bernstein, Johannes B Goll","doi":"10.1038/s41541-025-01072-6","DOIUrl":"10.1038/s41541-025-01072-6","url":null,"abstract":"<p><p>Transcriptomic signatures were identified in human peripheral blood mononuclear cells (PBMCs) and breast milk lymphocyte (BML) cells induced by trivalent inactivated influenza vaccine (TIV) or live attenuated influenza vaccine (LAIV) administered after delivery. We performed an RNA-Seq analysis on blood and breast milk samples from a subset of subjects enrolled in a randomized, double-blind controlled study in breastfeeding women who received either intranasal LAIV and intramuscular placebo, or intramuscular TIV and intranasal placebo (LAIV, n = 10 and TIV, n = 6). Differentially expressed genes, gene clusters, and enriched pathways were identified. We observed increased innate immune signaling responses in BML but not in PBMC at Day 28 for the LAIV group. We hypothesize that breastfeeding extended the innate response to LAIV via mucosal immunity. An association between an increased IgG antibody response in TIV vs. LAIV identified in the parent study using ELISA corresponded to IGHG1 immunoglobulin gene expression in Day 28 PBMCs.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"53"},"PeriodicalIF":6.9,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663773","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 : 2025-03-19DOI: 10.1038/s41541-025-01101-4
Anusyah Rathakrishnan, Ana Luisa Reis, Katy Moffat, Lynnette Goatley, Elisenda Viaplana, Jose Carlos Mancera, Alicia Urniza, Linda K Dixon
{"title":"Deletion of B125R increases protection induced by a genotype II African swine fever vaccine candidate.","authors":"Anusyah Rathakrishnan, Ana Luisa Reis, Katy Moffat, Lynnette Goatley, Elisenda Viaplana, Jose Carlos Mancera, Alicia Urniza, Linda K Dixon","doi":"10.1038/s41541-025-01101-4","DOIUrl":"10.1038/s41541-025-01101-4","url":null,"abstract":"<p><p>A modified live attenuated African swine fever genotype II virus, GΔDKE-CmutQ96R/K108D, with deletions of three genes, DP148R, EP153R, and K145R and expressing a mutated CD2v protein with a non-haemadsorbing phenotype, was further modified by first removing two reporter gene cassettes expressing fluorescent proteins. The B125R gene was then deleted and one reporter cassette was reinserted as a marker. Groups of pigs were immunised with this virus using a range of doses from 100 to 10,000 infectious particles. One pig immunised with the lowest dose reached a moderate severity humane endpoint. The other pigs showed mild or no clinical signs. Low levels of the virus used for immunisation were detected post-immunisation. After challenge with virulent virus, all pigs were protected, and few clinical signs were observed. Low levels of replication of the challenge virus were detected in seven from the twenty-three challenged pigs and no virus in the remaining pigs.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"52"},"PeriodicalIF":6.9,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143663767","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 : 2025-03-17DOI: 10.1038/s41541-025-01100-5
Aileen Ebenig, Mona V Lange, Michelle Gellhorn Serra, Alexandra Kupke, Roland Plesker, Bingqian Qu, Richard J P Brown, Thorsten J Maier, Michael D Mühlebach
{"title":"Differential efficacy of first licensed western vaccines protecting without immunopathogenesis Wuhan-1-challenged hamsters from severe COVID-19.","authors":"Aileen Ebenig, Mona V Lange, Michelle Gellhorn Serra, Alexandra Kupke, Roland Plesker, Bingqian Qu, Richard J P Brown, Thorsten J Maier, Michael D Mühlebach","doi":"10.1038/s41541-025-01100-5","DOIUrl":"10.1038/s41541-025-01100-5","url":null,"abstract":"<p><p>Four COVID-19 vaccines were developed, tested, and authorized early in Europe and the US. Comirnaty and Spikevax are mRNA-based, whereas Jcovden and Vaxzevria utilize adenoviral vectors (AdV). We described a hamster model of COVID-19 utilizing Wuhan-1 strain SARS-CoV-2, in which vaccine-associated immunopathogenesis can be induced by Alum-adjuvanted Spike protein (Alum+S). Such animals were vaccinated with the authorized vaccines or Alum+S, challenged, and examined. All vaccinated hamsters produced antibodies targeting S. Neutralizing antibodies (nAb) were induced only by authorized vaccines. While nAbs were present after one vaccination with AdV-vaccines, mRNA vaccines needed a boost immunization. Upon challenge, all authorized vaccines protected from severe disease. Less tissue damage and no live virus (one exception) were detectable in the lungs. In contrast, Alum+S immunized hamsters developed VAERD. Our data reveal the absence of induction of VAERD by early commercial vaccines in hamsters, while animals´ immune responses and protection seem to match the clinical vaccine efficacy.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"51"},"PeriodicalIF":6.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649597","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 randomized phase I trial of intranasal SARS-CoV-2 vaccine dNS1-RBD in children aged 3-17 years.","authors":"Kai Chu, Jiali Quan, Xiaohui Liu, Qi Chen, Xia Zang, Hanmin Jiang, Donglin Liu, Xiafei Chu, Chunlan Zhuang, Jinle Han, Xiangzhong Ye, Hongxing Pan, Shoujie Huang, Ting Wu, Jun Zhang, Ningshao Xia","doi":"10.1038/s41541-025-01096-y","DOIUrl":"10.1038/s41541-025-01096-y","url":null,"abstract":"<p><p>The intranasal SARS-CoV-2 vaccine dNS1-RBD (Pneucolin®), based on a live-attenuated influenza virus vector, has obtained Emergency Use Authorization in China for individuals aged 18 years and older. Here, we conducted a single-center, double-blind, placebo-controlled, age de-escalation phase 1 clinical trial to evaluate the safety of the dNS1-RBD in children aged 3-17 years (ChiCTR2300068044). Sixty-three participants received 2 intranasal doses of the vaccine or placebo at days 0 and 14. Safety assessments included adverse events/reactions within 30 days and serious adverse events (SAEs) over 12 months. Blood and nasal secretion samples were collected to further monitor blood indices and viral shedding. The vaccine group showed similar adverse reaction rates to the placebo group (39.0% vs 36.4%), with no SAEs related to vaccination. Data suggested that the dNS1-RBD vaccine is well-tolerated in children aged 3-17 years, and warrants further studies on its safety, immunogenicity and efficacy in this population.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"50"},"PeriodicalIF":6.9,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11914604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649552","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 : 2025-03-14DOI: 10.1038/s41541-025-01093-1
Raquel Munoz-Moreno, Viola Allaj, Eddie Gadee, Julie M Button, Fernando Diaz, Mohan S Maddur, Wei Chen, Cheng Hui Hu, Lyndsey Martinez, Andreas Giannakou, Adam Lee Campbell, Yana Miteva, Pengbo Guo, Bridget Huang, Shuai Shi, Jason Lotvin, Kristin Tompkins, Pirada Suphaphiphat Allen, Alicia Solórzano
{"title":"A highly stable lyophilized mRNA vaccine for Herpes Zoster provides potent cellular and humoral responses.","authors":"Raquel Munoz-Moreno, Viola Allaj, Eddie Gadee, Julie M Button, Fernando Diaz, Mohan S Maddur, Wei Chen, Cheng Hui Hu, Lyndsey Martinez, Andreas Giannakou, Adam Lee Campbell, Yana Miteva, Pengbo Guo, Bridget Huang, Shuai Shi, Jason Lotvin, Kristin Tompkins, Pirada Suphaphiphat Allen, Alicia Solórzano","doi":"10.1038/s41541-025-01093-1","DOIUrl":"10.1038/s41541-025-01093-1","url":null,"abstract":"<p><p>Herpes zoster (HZ) is a painful vesicular rash that occurs upon varicella-zoster virus (VZV) reactivation in older adults and immunocompromised individuals. Although there is currently an approved vaccine for the prevention of shingles, its administration is commonly associated with high reactogenicity. This highlights the need to develop new vaccine alternatives with long lasting immunity and improved tolerability upon administration. In the present study, 10 different vaccine candidate designs using two different codon optimizations targeting the VZV glycoprotein E (gE) were generated. A subset of mRNA constructs were formulated into lipid nanoparticles and assessed for their ability to induce specific cellular and humoral immune responses following vaccination in mice. Notably, the selected mRNA vaccine candidates induced high levels of antibodies and robust CD4<sup>+</sup> but also CD8<sup>+</sup> immune responses. Moreover, we showed that our alternate lyophilized vaccine provides comparable immunogenicity to current liquid frozen formulations and is stable under long-term storage conditions.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"49"},"PeriodicalIF":6.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11909110/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634230","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 : 2025-03-13DOI: 10.1038/s41541-024-01044-2
Desalegn W Kifle, Mumtaz Y Balkhi, Yasuko Ono, Jenn Davis, Naoko Doi, Aryandra Arya, Jiho Kim, Aravindan Kalyanasundaram, Sourav Nandy, Njariharinjakamampionona Rakotozandrindrainy, Bart Staker, Justin Craig, Raphaël Rakotozandrindrainy, Birkneh T Tadesse, Florian Marks, Lisa Jackson, Darrick Carter, Sean A Gray, Afzal A Siddiqui
{"title":"A functional enzymatic assay as potential readout for a clinical trial of a schistosomiasis vaccine.","authors":"Desalegn W Kifle, Mumtaz Y Balkhi, Yasuko Ono, Jenn Davis, Naoko Doi, Aryandra Arya, Jiho Kim, Aravindan Kalyanasundaram, Sourav Nandy, Njariharinjakamampionona Rakotozandrindrainy, Bart Staker, Justin Craig, Raphaël Rakotozandrindrainy, Birkneh T Tadesse, Florian Marks, Lisa Jackson, Darrick Carter, Sean A Gray, Afzal A Siddiqui","doi":"10.1038/s41541-024-01044-2","DOIUrl":"10.1038/s41541-024-01044-2","url":null,"abstract":"<p><p>An estimated 200 million people are currently infected with schistosomiasis and an additional 800 million reside in high transmission-risk areas in 78 endemic countries. In this report we describe a functional enzymatic assay based on the core calpain antigen (Sm-p80) of the schistosomiasis vaccine, SchistoShield®. A 44 kDa soluble variant of the core Sm-p80 antigen (B7), was assessed for its enzymatic activity using a fluorescent synthetic substrate. Inhibition of the B7 enzymatic activity by Sm-p80-specific antibodies obtained from pre-clinical trials in rodents, non-human primates as well as from participants of the human clinical trials was measured. The B7 enzyme activity followed a Michaelis-Menten-like kinetic behavior. Statistically significant inhibition of the B7 activity was observed by Sm-p80-specific antibodies produced by immunized mice, non-human primates and humans. This quantitative serological assay could be of value in assessing the effectiveness of the SchistoShield® vaccine in human trials in Africa.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"48"},"PeriodicalIF":6.9,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143625531","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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