NPJ Vaccines最新文献

{"title":"Stabilization of norovirus GII.3 virus-like particles by rational disulfide engineering.","authors":"Christopher Warren, Jennifer D Galli, Karin Bystol, Gregory O'Donnell, Andrew R Swartz, Emily A Dewar, Corey May Fulton, Pamela Shen, Estibaliz Gonzalez-Fernandez, Lizzy Aurora DeWitt, Uijin Jeong, Oscar Chi-Chien Pan, Sean Miller, Arthur Fridman, Courtney David, Zhifeng Chen, Jiajie Wei","doi":"10.1038/s41541-025-01254-2","DOIUrl":"10.1038/s41541-025-01254-2","url":null,"abstract":"<p><p>Noroviruses are non-enveloped, single-stranded positive-sense RNA viruses and the leading cause of gastroenteritis worldwide. The major capsid protein, VP1, can self-assemble into non-infectious virus-like particles (VLPs), representing an attractive vaccine platform. It was demonstrated that engineered disulfide bonds within VP1 could significantly stabilize VLPs of the archetypal GI.1 strain. Here, we apply a similar strategy to VLPs of multiple circulating GII genotypes. We find that engineered disulfide mutations can significantly stabilize VLPs of the GII.3 strain, but not the closely related GII.6 strain. Disulfide-stabilized GII.3 VLPs (GII.3-DS1) exhibit increased yields, greater homogeneity, and higher thermal stability compared to wild-type GII.3 VLPs. GII.3-DS1 VLPs are a superior reagent in immunological assays compared to the wild-type counterpart. Importantly, mRNA encoding GII.3-DS1 elicits superior humoral immune responses compared to wild-type GII.3 mRNA in mice. These results demonstrate the utility of rational VLP stabilization for advancing vaccine development efforts.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"196"},"PeriodicalIF":6.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883335","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":"Immunogenicity and safety of a rabies-based highly pathogenic influenza A virus H5 vaccine in cattle.","authors":"Nir Paran, Christoph Wirblich, Catherine Olal, Alessandro Tarquinio, Kimberly H Lohmeyer, Drishya Kurup, Stacey Schultz-Cherry, Ismaila Shittu, Gregory C Gray, Dennis A Bente, Pia U Olafson, Matthias J Schnell","doi":"10.1038/s41541-025-01238-2","DOIUrl":"10.1038/s41541-025-01238-2","url":null,"abstract":"<p><p>The circulation of highly pathogenic H5 influenza A viruses in cattle, other mammals, and wildlife threatens animal and human health. To address this, we vaccinated heifer-calves with a deactivated rabies-virus-based H5 vaccine, which was well-tolerated and elicited neutralizing antibodies against both clade-1 and clade-2.3.4.4b H5N1 viruses, comparable to naturally H5-infected and convalescing cows. The immune responses to the vaccine platform were durable for at least 200 days and unaffected by preexisting RABV immunity.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"197"},"PeriodicalIF":6.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144883334","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":"Proteogenomic approach to immunopeptidomics of ovarian tumors identifies shared peptide vaccine candidates.","authors":"Jacopo Chiaro, Karita Peltonen, Kadri Õunap, Aubrey Bailey, Sara Feola, Sara Wojciechowski, Masoumeh Es-Haghi, Mikel Azkargorta, Félix Elortza, Salvatore Russo, Hanna Sallinen, Maarit Anttila, Olga Gurvich, Vincenzo Cerullo, Tuija Kekarainen","doi":"10.1038/s41541-025-01234-6","DOIUrl":"10.1038/s41541-025-01234-6","url":null,"abstract":"<p><p>Epithelial ovarian cancers are largely comprised of immunogenic tumor sub-types with the degree of CD8+ T cell infiltration being prognostic of clinical outcome. Tumor antigen-specific T cells are identified among these infiltrating T cell populations which has spurred a decade of development towards antigen-specific immunotherapies. Despite these efforts, the success of such immunotherapies has shown to be limited. In this study, we used state-of-the art immunopeptidomics approach and a novel proteogenomic profiling method to identify potential immunogenic human leukocyte antigen class I-presented peptides from patient-derived high-grade serous ovarian cancer. From 11 patients' tumors, we identified promising candidates for their therapeutic potential. Of these, we selected the best 13 candidates and validated their immunogenicity in both healthy donors and cancer patients.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"195"},"PeriodicalIF":6.5,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357944/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862362","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":"Enterovirus A71 priorities, challenges, and future opportunities in humoral immunity and vaccine development.","authors":"Amanda Makha Bifani, Han Kang Tee, Aleksandar Antanasijevic, Sophie Clément, Caroline Tapparel","doi":"10.1038/s41541-025-01184-z","DOIUrl":"10.1038/s41541-025-01184-z","url":null,"abstract":"<p><p>Enterovirus A71 (EV-A71) is a significant public health concern, particularly in the Asia-Pacific region, where it commonly causes hand, foot, and mouth disease outbreaks. There are no clinically available antivirals, and use of inactivated vaccine is restricted to China. This review explores patterns of humoral immune response to EV-A71, highlights critical epitopes, and discusses vaccine development. Critically, we examine the challenges facing EV vaccination strategies, as well as future directions.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"194"},"PeriodicalIF":6.5,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356949/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859400","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 self-amplifying mRNA vaccine expressing PRV gD induces robust immunity against virulent mutants.","authors":"Tong Ling, Zhang Xin, Li Huan-Huan, Zheng Ya-Ting, Liu Ya-Mei, Guo Rong-Li, Armando Mario Damiani, Chen Sai-Sai, Zhang Chuan-Jian, Duan Rui, Mao Shu-Yu, Yu Jia-Li, Zhang Qian-Qian, Tao Ruo-Nan, Nikolaus Osterrieder, Xia Shu-Hua, Wang Ji-Chun","doi":"10.1038/s41541-025-01251-5","DOIUrl":"10.1038/s41541-025-01251-5","url":null,"abstract":"<p><p>Pseudorabies virus (PRV) causes an acute febrile infectious disease of pigs. Since 2011, PRV variants have appeared and spread nationwide in China. mRNA vaccines present a safe alternative and can stimulate humoral and cellular immunity. We constructed a self-amplifying mRNA (saRNA) vaccine containing gD gene of a highly virulent PRV variant. In mice, the PRV saRNA gD vaccine induced high levels of neutralizing antibodies. In piglets, vaccination with the PRV saRNA gD vaccine at a dose of as little as 5 μg induced very strong humoral immunity and cellular immunity, providing full protection against challenge infection with very virulent PRV variants. Protection following vaccination with saRNA gD induced significantly stronger protection than attenuated live vaccines and inactivated vaccines. In addition, our results confirm that a PRV saRNA vaccine expressing only one antigen can induce excellent protection in weaned piglets. Hence, the PRV saRNA gD vaccine might be a very promising substitute for inactivated and live vaccines. Finally, we provide proof-of-concept for the development of self-amplifying mRNA vaccines for members of the Alphaherpesvirinae, including herpes simplex virus 1 and 2 as well as varicella zoster virus.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"193"},"PeriodicalIF":6.5,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354905/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855920","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":"Pregnancy reduces COVID-19 vaccine immunity against novel variants.","authors":"Maclaine A Parish, Jaiprasath Sachithanandham, Lizeth Gutierrez, Han-Sol Park, Anna Yin, Katerina Roznik, Patrick Creisher, John S Lee, Laura A St Clair, Annie Werner, Catherine Pilgrim-Grayson, Lea Berhane, Hana Golding, Patrick Shea, Katherine Fenstermacher, Richard Rothman, Irina Burd, Jeanne Sheffield, Andrea L Cox, Andrew Pekosz, Sabra L Klein","doi":"10.1038/s41541-025-01236-4","DOIUrl":"10.1038/s41541-025-01236-4","url":null,"abstract":"<p><p>Pregnant women are at heightened risk for severe outcomes from infectious diseases like COVID-19, yet were not included in initial vaccine trials, which may contribute to low booster uptake (15% or lower). We explored the serological and cellular responses to COVID-19 mRNA booster vaccines (i.e., ancestral and BA.5) in pregnant and age-matched, non-pregnant females to identify how pregnancy affects immunity against the vaccine and novel variants. Antibodies from pregnant women were less cross-reactive to non-vaccine antigens, including XBB.1.5 and JN.1. Non-pregnant females showed greater IgG1:IgG3 ratios and neutralization against all variants. In contrast, pregnant women had lower IgG1:IgG3 ratios and neutralization but increased antibody-dependent NK cell cytokine production and neutrophil phagocytosis, especially against novel variants. Pregnancy increased memory CD4+ T cells, IFNγ production, monofunctional dominance, and fatty acid oxidation. Pregnancy may reduce the breadth, composition, and magnitude of humoral and cellular immunity, particularly in response to novel variants.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"191"},"PeriodicalIF":6.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144847976","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 platform approach as a plausible option for nonclinical safety assessment of adjuvanted vaccines.","authors":"Eric Destexhe","doi":"10.1038/s41541-025-01245-3","DOIUrl":"10.1038/s41541-025-01245-3","url":null,"abstract":"<p><p>Vaccine platform technologies are reproducible, standardized manufacturing and development methods that may be leveraged to streamline regulatory approval of new vaccines. To evaluate the plausibility of a platform approach for the nonclinical safety assessment of adjuvanted recombinant-protein vaccine candidates, a comparative analysis was performed on repeat-dose toxicity data of four AS01 adjuvanted candidate vaccines from five rabbit studies. Groups of animals received AS01-adjuvanted vaccines, AS01 alone, or antigens alone on multiple occasions. All vaccines were well-tolerated, showing mainly transient signs of inflammation after the administrations, consistent across all vaccines and similar to AS01. The antigens alone induced only minimal signs of inflammation, indicating that AS01 mainly drives the innate immune response. These findings support the plausibility of a platform approach for the nonclinical safety assessment of adjuvanted vaccines, potentially reducing animal use and expediting first-in-human trials by streamlining or eliminating some nonclinical studies.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"192"},"PeriodicalIF":6.5,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12350924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144847975","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":"Immunologic profiling of the infant immune response to whole-cell and acellular pertussis vaccines.","authors":"C Buddy Creech, Mariana Leguia, Johannes B Goll, Leigh M Howard, Antón Vila-Sanjurjo, Sandra Yoder, Diana Juarez, Alejandra Garcia-Glaessner, Casey E Gelber, Natalia Jimenez-Truque, Sami Cherikh, Ana I Gil, James E Crowe, Rubelio Cornejo Cotos, Kathryn M Edwards, Claudio F Lanata","doi":"10.1038/s41541-025-01170-5","DOIUrl":"10.1038/s41541-025-01170-5","url":null,"abstract":"<p><p>Despite robust antibody responses, immunity induced by acellular pertussis vaccine (DTaP) wanes over time and risk of pertussis seems to be lower in children who receive whole-cell vaccine (DTP) as their first dose. To interrogate the early immunologic response to pertussis vaccine, we enrolled 56 healthy infants who received either DTP or DTaP at 2-, 4-, 6-, and 18-months of age. RNA-sequencing and ribosome profiling of PBMC were performed prior to vaccination (Day 1) and on either Day 2 or Day 8. Pathway enrichment analysis on Days 2 and 8 showed enrichment of TLR-signaling and FcϒR-mediated phagocytosis among DTP recipients. DTP also led to increases in IRAK-4 and IL-1ß. After booster vaccination, a higher frequency of PT-specific B-cells was observed in DTP- vs. DTaP recipients. These data provide insights into the early immunologic responses to pertussis vaccine and may guide next-generation pertussis vaccine development.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"189"},"PeriodicalIF":6.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12340008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822142","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":"Systems biology-based assessment of immune responses to whole cell and acellular pertussis vaccines.","authors":"Mariana Leguia, Antón Vila-Sanjurjo, Diana Juarez, Alejandra Garcia-Glaessner, Ana I Gil, Mayita Alvarez, Rubelio Cornejo, Sami Cherikh, Casey E Gelber, Johannes B Goll, Leigh M Howard, Natalia Jimenez-Truque, Kathryn M Edwards, C Buddy Creech, Claudio F Lanata","doi":"10.1038/s41541-025-01121-0","DOIUrl":"10.1038/s41541-025-01121-0","url":null,"abstract":"<p><p>Given the local and systemic adverse reactions associated with whole-cell pertussis vaccines combined with diphtheria and tetanus toxoids (DTP), acellular pertussis vaccines combined with the same toxoids (DTaP) were developed in the 1990s. In comparison to DTP, DTaP vaccines demonstrated reduced reactogenicity and equivalent or improved immunogenicity and efficacy. However, there has been a resurgence of pertussis disease, particularly in DTaP-vaccinated children, suggesting that immunity wanes more quickly with DTaP vaccination. To elucidate the differences in immune responses to DTP and DTaP vaccines, we employed a systems biology-based strategy to compare global changes in gene expression following primary vaccination with either DTP or DTaP. We used RNA-Seq and ribosome profiling (RP) to identify transcriptional and translational signatures, respectively, in peripheral blood mononuclear cells (PBMCs) collected from 50 infant recipients of DTP or DTaP at two time-points (baseline (pre-vaccination at Day 1) and either Day 2 or 8 post-vaccination). We also used standard serologic methods to assess immunogenicity, and correlated these results with transcriptional and translational signatures. Here, we provide a detailed description of the rationale, experimental design, methodology, and enrollment procedures used. Given the technical complexity of our approach, our objective is to fill knowledge gaps, describe key quality metrics, and support future publications. In brief, we recovered 4-12 million PBMCs (average 8.9 million) with 99% viability per 2.5 mL blood sample, enabling excellent nucleic acid recovery yields for the preparation of high-quality sequencing libraries. In turn, these generated RNA-Seq and RP datasets with sufficient genome coverage breadth and depth to enable differential gene expression analyses, demonstrating the validity of this approach to study pertussis vaccine immunology specifically, and its utility to characterize mechanisms of the human immune response to vaccination generally.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"188"},"PeriodicalIF":6.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12340147/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822144","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":"Safety and efficacy of a novel glycoengineered recombinant vaccine candidate against Haemonchus contortus in sheep.","authors":"Floriana Sajovitz-Grohmann, Isabella Adduci, Dirk Werling, Sandra Wiedermann, Licha N Wortha, Bojan Prole, Julia Zlöbl, Jolina Elster, Alexander Tichy, Anja Joachim, Thomas Wittek, Barbara Hinney, Shi Yan, Katharina Lichtmannsperger","doi":"10.1038/s41541-025-01249-z","DOIUrl":"10.1038/s41541-025-01249-z","url":null,"abstract":"<p><p>Haemonchus contortus is a highly pathogenic nematode in small ruminants, causing major production losses and animal welfare concerns. With increasing anthelmintic resistance, vaccination offers a more sustainable control strategy. This study evaluated a novel glycoengineered vaccine produced in Hi5 insect cells in a randomized, controlled trial including Jura × Lacaune sheep. Animals received either Barbervax^® (BVAX), the glycoengineered vaccine (GEA) composed of five antigens (H11, H11-1, H11-2, H11-4 and GA1), its non-glycoengineered counterpart (NEA), or served as controls. Over 16 weeks, clinical, immunological, and parasitological data were collected. GEA reduced fecal egg counts by 81.09% and worm burden by 25.36%, showing a lower degree of anemia compared to NEA and control. All vaccinated groups exhibited elevated IgG/IgE responses. The results underscore the importance of glycoengineering in achieving protective immunity against H. contortus, supporting the development of highly effective recombinant vaccines against this and other parasitic worms in the future.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"190"},"PeriodicalIF":6.5,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12339958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144822143","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}