NPJ VaccinesPub Date : 2025-08-30DOI: 10.1038/s41541-025-01258-y
Francisca Villanueva-Flores, Javier I Sanchez-Villamil, Igor Garcia-Atutxa
{"title":"AI-driven epitope prediction: a system review, comparative analysis, and practical guide for vaccine development.","authors":"Francisca Villanueva-Flores, Javier I Sanchez-Villamil, Igor Garcia-Atutxa","doi":"10.1038/s41541-025-01258-y","DOIUrl":"10.1038/s41541-025-01258-y","url":null,"abstract":"<p><p>Integrating AI into epitope prediction is transforming vaccine design by delivering unprecedented accuracy, speed, and efficiency. This review synthesizes recent breakthroughs particularly CNNs, transformers, and GNNs highlighting experimentally validated models like MUNIS and GraphBepi that reveal previously overlooked epitopes. By benchmarking AI tools against traditional methods, we identify structural data integration as pivotal, offering practical strategies to translate computational predictions into actionable experimental workflows for next-generation vaccines.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"207"},"PeriodicalIF":6.5,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12398602/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963212","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 : 2025-08-29DOI: 10.1038/s41541-025-01250-6
Belén Borrego, Celia Alonso, Sandra Moreno, Eva Calvo-Pinilla, Gema Lorenzo, Pedro J Sánchez-Cordón, Alejandro Brun
{"title":"The 40Fp8 vaccine strain is safe and protects pregnant ewes from a virulent RVFV challenge.","authors":"Belén Borrego, Celia Alonso, Sandra Moreno, Eva Calvo-Pinilla, Gema Lorenzo, Pedro J Sánchez-Cordón, Alejandro Brun","doi":"10.1038/s41541-025-01250-6","DOIUrl":"10.1038/s41541-025-01250-6","url":null,"abstract":"<p><p>In the present study, we evaluated the immunogenicity, safety and protective efficacy of the attenuated RVFV-40Fp8 strain in natural hosts (non-pregnant ewes) and in a highly susceptible host infection model such as pregnant ewes in the first third of pregnancy. Our results confirm the immunogenicity of 40Fp8 administration in non-pregnant and pregnant ewes, as well as the absence of foetal damage even after a high-dose vaccination regime in pregnant ewes. In addition, the ewes and their foetuses were protected against a virulent RVFV-56/74 strain challenge, as shown by comparative evaluation of blood, serum and different tissue samples from vaccinated and non-vaccinated pregnant ewes. These results confirm the potential use of 40Fp8 as a RVF live-attenuated vaccine candidate and pave the way for further clinical developments.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"206"},"PeriodicalIF":6.5,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963160","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 : 2025-08-28DOI: 10.1038/s41541-025-01257-z
Jade Pattyn, Odile Launay, Robert Steffen, Birgit Weinberger, Giovanni Gabutti, Alojz Ihan, Thomas Weinke, Ligita Jancoriene, Paolo Bonanni, Pierre Van Damme
{"title":"Author Correction: Overview of vaccines for adults authorized, recommended, and implemented in the European Union.","authors":"Jade Pattyn, Odile Launay, Robert Steffen, Birgit Weinberger, Giovanni Gabutti, Alojz Ihan, Thomas Weinke, Ligita Jancoriene, Paolo Bonanni, Pierre Van Damme","doi":"10.1038/s41541-025-01257-z","DOIUrl":"10.1038/s41541-025-01257-z","url":null,"abstract":"","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"205"},"PeriodicalIF":6.5,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12394423/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963194","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 : 2025-08-27DOI: 10.1038/s41541-025-01255-1
Qisi Zhang, Jiahui Cheng, Jihuan Hou, Yinlei Su, Le Li, Le Tong, Jing Li, Quan Shen, Zihao Wang, Minqi Wu, Zhen Li, Qikai Wang, Yunfei Zhang, Rui Sun, Longlong Si
{"title":"Synthetic biology-inspired development of live attenuated influenza vaccines.","authors":"Qisi Zhang, Jiahui Cheng, Jihuan Hou, Yinlei Su, Le Li, Le Tong, Jing Li, Quan Shen, Zihao Wang, Minqi Wu, Zhen Li, Qikai Wang, Yunfei Zhang, Rui Sun, Longlong Si","doi":"10.1038/s41541-025-01255-1","DOIUrl":"10.1038/s41541-025-01255-1","url":null,"abstract":"<p><p>Live attenuated influenza vaccines (LAIVs) provide robust, cross-protective immunity but have traditionally been developed empirically and are associated with safety concerns. Recent advances in rational design enable precise genetic modifications to enhance safety and immunogenicity. This review highlights key molecular strategies advancing next-generation LAIV development and their potential to accelerate the production of safer, more effective vaccines against seasonal and pandemic influenza.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"204"},"PeriodicalIF":6.5,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12391339/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963193","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 : 2025-08-26DOI: 10.1038/s41541-025-01256-0
Sung K Chiu, Eliska Furlong, Elizabeth J McKinnon, Annette Fox, Stephany Sánchez Ovando, Louise Carolan, Andrew McLean-Tooke, Joyce Oommen, Daniel K Yeoh, Laurence C Cheung, Nicholas G Gottardo, Rishi S Kotecha
{"title":"Boosting the influenza vaccine schedule in children with cancer: a prospective open-label study.","authors":"Sung K Chiu, Eliska Furlong, Elizabeth J McKinnon, Annette Fox, Stephany Sánchez Ovando, Louise Carolan, Andrew McLean-Tooke, Joyce Oommen, Daniel K Yeoh, Laurence C Cheung, Nicholas G Gottardo, Rishi S Kotecha","doi":"10.1038/s41541-025-01256-0","DOIUrl":"10.1038/s41541-025-01256-0","url":null,"abstract":"<p><p>Current immunization guidelines recommend one dose of influenza vaccine for children aged ≥9 years and two doses for younger or vaccine-naïve children. However, children receiving chemotherapy have an attenuated immune response. We performed a prospective open-label study in children undergoing treatment for cancer at Perth Children's Hospital, Western Australia, to examine the safety and efficacy of a boosted influenza schedule. This comprised three vaccine doses for children <9 years of age and two doses for those ≥9 years, with each dose administered at least 4 weeks apart. The additional vaccine dose was well-tolerated with no serious adverse events reported; it also resulted in improved geometric mean antibody titres for A/H1N1 (70 to 97, p = 0.003), A/H3N2 (76 to 104, p = 0.003) and B/Washington (148 to 179, p = 0.03) strains. In summary, a boosted influenza vaccine schedule is safe and improves humoral immune response, providing a readily implementable strategy to protect children undergoing treatment for cancer.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"203"},"PeriodicalIF":6.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12379222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963156","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 : 2025-08-22DOI: 10.1038/s41541-025-01231-9
Caroline Chupin, Pauline Brun, Marjorie Ray, Chloé Mialon, Maëlle Reitano, Aurélien Traversier, Emilie Laurent, Abdelghafar Goumaidi, Julien Fouret, Stéphane Paul, Marina Boukhvalova, Kevin Yim, Jorge Blanco, Marie-Eve Hamelin, Guy Boivin, Manuel Rosa-Calatrava, Julia Dubois
{"title":"Metavac-RSV mucosal bivalent vaccine candidate protects cotton rats against pneumoviruses and is produced using serum-free cell culture in bioreactor.","authors":"Caroline Chupin, Pauline Brun, Marjorie Ray, Chloé Mialon, Maëlle Reitano, Aurélien Traversier, Emilie Laurent, Abdelghafar Goumaidi, Julien Fouret, Stéphane Paul, Marina Boukhvalova, Kevin Yim, Jorge Blanco, Marie-Eve Hamelin, Guy Boivin, Manuel Rosa-Calatrava, Julia Dubois","doi":"10.1038/s41541-025-01231-9","DOIUrl":"10.1038/s41541-025-01231-9","url":null,"abstract":"<p><p>Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are the main etiologic agents of viral bronchiolitis and pneumonia in children and the elderly. As live-attenuated vaccines (LAV) can stimulate robust mucosal and cellular responses, we previously engineered an HMPV-based bivalent LAV Metavac®-RSV candidate and reported its capacity to protect mice against HMPV and RSV challenges after intranasal delivery. To progress towards clinical development, we identified a GMP-grade Vero cell platform as permissive and efficient to produce high yields of functional Metavac®-RSV, expressing both RSV and HMPV F antigen after several passages. Metavac®-RSV protected cotton rats against both HMPV and RSV challenges, significantly reducing viral replication in the respiratory airways and inducing high titers of neutralizing antibodies. Finally, we identified process parameters to scale-up the production process of Metavac®-RSV using Vero cells cultivated on microcarriers in a 2 L single-use stirred-tank bioreactor, with a scalable upstream production process amenable to industrial manufacturing.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"202"},"PeriodicalIF":6.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12373873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963197","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 : 2025-08-20DOI: 10.1038/s41541-025-01218-6
Shridhar Bale, Elena Gustchina, Javier Guenaga, Victor Ayala, Wen-Hsin Lee, Gabriel Ozorowski, Stephen Whitney, Richard Wilson, Sabyasachi Baboo, Jolene K Diedrich, Esmeralda D Doyle, Lauren Hudacik, Elana Ben-Akiva, Kristen A Rodrigues, Darrell J Irvine, John R Yates, James C Paulson, Andrew B Ward, Timothy Fouts, Richard T Wyatt
{"title":"Accelerated cGMP production of near-native HIV-1 Env trimers following electroporation transfection and immunogenicity analysis.","authors":"Shridhar Bale, Elena Gustchina, Javier Guenaga, Victor Ayala, Wen-Hsin Lee, Gabriel Ozorowski, Stephen Whitney, Richard Wilson, Sabyasachi Baboo, Jolene K Diedrich, Esmeralda D Doyle, Lauren Hudacik, Elana Ben-Akiva, Kristen A Rodrigues, Darrell J Irvine, John R Yates, James C Paulson, Andrew B Ward, Timothy Fouts, Richard T Wyatt","doi":"10.1038/s41541-025-01218-6","DOIUrl":"10.1038/s41541-025-01218-6","url":null,"abstract":"<p><p>Evaluation of recombinant HIV-1 surface glycoproteins (Env) as vaccine candidates for Phase I human experimental trials often requires production of cGMP-grade well-ordered Env trimers. Here, we report an accelerated cGMP compatible approach for expression and purification of a stabilized HIV clade C-derived trimer '16055 DG4 NFL' (for native flexibly linked). This recombinant trimer was expressed from CHO-S™ cells using a MaxCyte® VLX™ electroporation-based transient transfection process. The 16055 DG4 NFL was designed with multiple internal stabilizing mutations and, as well, deletion of four N-linked glycans (DG4) proximal to the CD4 binding site (CD4bs) engineered to improve B cell recognition of this conserved neutralizing determinant. The transient process circumvents the need to develop stable cell lines expressing the Env trimers that is often the most time-consuming step impacting vaccine development timelines. The 16055 DG4 NFL trimer was purified by immunoaffinity chromatography using the broadly neutralizing antibody (bNAb), PGT145. Following additional downstream processing steps, purified trimer was vialed, frozen and stored at -80 °C. Upon thaw and analysis, the trimer displayed homogeneity and a near-native conformation as determined by size-exclusion chromatography (SEC), negative stain and cryo-electron microscopy (EM), differential scanning calorimetry (DSC) and biolayer interferometry (BLI). The immunogenicity of the trimer was tested in rabbits with bolus, escalating dose and divided dose immunization regimens. Rabbits from all three regimens elicited tier 2 autologous neutralizing antibodies that targeted the exposed protein region at the CD4bs. The trimer is currently under investigation in a human clinical trial (NCT06332339) for safety, tolerability and as a priming candidate followed by heterologous boosting to potentially elicit cross-neutralizing antibodies.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"198"},"PeriodicalIF":6.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963238","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 : 2025-08-20DOI: 10.1038/s41541-025-01252-4
Payal P Pratap, Christopher A Cottrell, James Quinn, Diane G Carnathan, Daniel L V Bader, Andy S Tran, Chiamaka A Enemuo, Julia T Ngo, Sara T Richey, Hongmei Gao, Xiaoying Shen, Kelli M Greene, Jonathan Hurtado, Katarzyna Kaczmarek Michaels, Elana Ben-Akiva, Ashley Lemnios, Mariane B Melo, Joel D Allen, Gabriel Ozorowski, Max Crispin, Bryan Briney, David Montefiori, Guido Silvestri, Darrell J Irvine, Shane Crotty, Andrew B Ward
{"title":"Immunofocusing on the conserved fusion peptide of HIV envelope glycoprotein in rhesus macaques.","authors":"Payal P Pratap, Christopher A Cottrell, James Quinn, Diane G Carnathan, Daniel L V Bader, Andy S Tran, Chiamaka A Enemuo, Julia T Ngo, Sara T Richey, Hongmei Gao, Xiaoying Shen, Kelli M Greene, Jonathan Hurtado, Katarzyna Kaczmarek Michaels, Elana Ben-Akiva, Ashley Lemnios, Mariane B Melo, Joel D Allen, Gabriel Ozorowski, Max Crispin, Bryan Briney, David Montefiori, Guido Silvestri, Darrell J Irvine, Shane Crotty, Andrew B Ward","doi":"10.1038/s41541-025-01252-4","DOIUrl":"10.1038/s41541-025-01252-4","url":null,"abstract":"<p><p>During infection, the fusion peptide (FP) of HIV envelope glycoprotein (Env) serves a central role in viral fusion with the host cell. As such, the FP is highly conserved and therefore an attractive epitope for vaccine design. Here, we describe a vaccination study in non-human primates (NHPs) where glycan deletions were made on soluble HIV Env to increase FP epitope exposure. When delivered via implantable osmotic pumps, this immunogen primed immune responses against the FP, which were then boosted with heterologous trimers resulting in a focused immune response targeting the conserved FP epitope. Although autologous immunizations did not elicit high affinity FP-targeting antibodies, the conserved FP epitope on a heterologous trimer further matured the lower affinity, FP-targeting B cells. This study suggests using epitope conservation strategies on distinct Env trimer immunogens can focus humoral responses on desired neutralizing epitopes and suppress immune-distracting antibody responses against non-neutralizing epitopes.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"200"},"PeriodicalIF":6.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963202","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":"Trehalose-loaded LNPs enhance mRNA stability and bridge in vitro in vivo efficacy gap.","authors":"Xu-Han Liu, Hui-Ping Song, Ling-Ling Tao, Zhe Zhai, Jin-Xing Huang, Yong-Xian Cheng","doi":"10.1038/s41541-025-01253-3","DOIUrl":"10.1038/s41541-025-01253-3","url":null,"abstract":"<p><p>Lyophilization enhances mRNA vaccine stability, but conventional approaches using external trehalose for lipid nanoparticle (LNP) colloidal stability neglect mRNA chemical degradation and are compromised in vivo efficacy. Here, we report a dual-function trehalose strategy integrating its external and internal roles within LNP. This strategy enables trehalose to externally form a vitrified matrix that preserves LNP colloidal integrity, while internally stabilizing mRNA through hydrogen bonding, markedly reducing chemical degradation during storage compared to LNP relying solely on externally added trehalose. Crucially, co-loaded trehalose is co-delivered into cells, bridging the in vitro-in vivo gap by mitigating oxidative stress through reduced reactive oxygen species (ROS) and malondialdehyde (MDA) alongside elevated glutathione (GSH) and superoxide dismutase (SOD). This is corroborated by downregulated cytoplasmic and nuclear nuclear factor erythroid 2-related factor 2 (Nrf2) expression. Our strategy provides a simple, universally adaptable, and scalable method to enhance mRNA-LNP formulations stability without exogenous components or complex lyophilization steps.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"201"},"PeriodicalIF":6.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963157","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 : 2025-08-20DOI: 10.1038/s41541-025-01169-y
Michael N Pensiero
{"title":"Accelerating the manufacturing of HIV Env protein vaccines for early phase clinical evaluation.","authors":"Michael N Pensiero","doi":"10.1038/s41541-025-01169-y","DOIUrl":"10.1038/s41541-025-01169-y","url":null,"abstract":"","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"199"},"PeriodicalIF":6.5,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12368038/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144963163","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}