NPJ VaccinesPub Date : 2025-03-12DOI: 10.1038/s41541-025-01102-3
Changyoun Kim, Armine Hovakimyan, Karen Zagorski, Tatevik Antonyan, Irina Petrushina, Hayk Davtyan, Gor Chailyan, Jonathan Hasselmann, Michiyo Iba, Anthony Adame, Edward Rockenstein, Marcell Szabo, Mathew Blurton-Jones, David H Cribbs, Anahit Ghochikyan, Eliezer Masliah, Michael G Agadjanyan
{"title":"Retraction Note: Efficacy and immunogenicity of MultiTEP-based DNA vaccines targeting human α-synuclein: prelude for IND enabling studies.","authors":"Changyoun Kim, Armine Hovakimyan, Karen Zagorski, Tatevik Antonyan, Irina Petrushina, Hayk Davtyan, Gor Chailyan, Jonathan Hasselmann, Michiyo Iba, Anthony Adame, Edward Rockenstein, Marcell Szabo, Mathew Blurton-Jones, David H Cribbs, Anahit Ghochikyan, Eliezer Masliah, Michael G Agadjanyan","doi":"10.1038/s41541-025-01102-3","DOIUrl":"10.1038/s41541-025-01102-3","url":null,"abstract":"","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"47"},"PeriodicalIF":6.9,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11903769/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143616562","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 : 2025-03-06DOI: 10.1038/s41541-025-01099-9
Erwin van den Born, Ferenc Olasz, István Mészáros, Eszter Göltl, Barbara Oláh, Jui Joshi, Emma van Kilsdonk, Ruud Segers, Zoltán Zádori
{"title":"African swine fever virus vaccine strain Asfv-G-∆I177l reverts to virulence and negatively affects reproductive performance.","authors":"Erwin van den Born, Ferenc Olasz, István Mészáros, Eszter Göltl, Barbara Oláh, Jui Joshi, Emma van Kilsdonk, Ruud Segers, Zoltán Zádori","doi":"10.1038/s41541-025-01099-9","DOIUrl":"10.1038/s41541-025-01099-9","url":null,"abstract":"<p><p>ASFV-G-ΔI177L is a modified-live African swine fever virus (ASFV) strain that has been incorporated into a commercially available vaccine. Its safety in pregnant sows and genetic stability in an in vivo passaging experiment were investigated. Upon inoculation of two pregnant sows with ASFV-G-ΔI177L, one developed moderate ASF-related clinical signs. In terms of reproductive performance, 43% of the offspring was born dead and the live-born piglets developed ASF-specific clinical signs, became viremic, and only 17% survived until the end of study. During passaging in pigs, ASFV-G-ΔI177L reverted to virulence with severe ASF-specific clinical signs at passages 3 and 4, associated with increased viremia. Whole genome sequencing identified C257L mutations as a potential driver of increased replication fitness and virulence. The data show that ASFV-G-ΔI177L is not genetically stable and, therefore not safe for use in ASF vaccines and suggest that ASF vaccine candidates should be tested for safety in pregnant animals.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"46"},"PeriodicalIF":6.9,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11885574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573342","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 : 2025-03-05DOI: 10.1038/s41541-025-01092-2
Yugenia K Hong-Nguyen, Joseph Toerner, Lucia Lee, Maria C Allende, David C Kaslow
{"title":"Author Correction: Regulatory review of benefits and risks of preventing infant RSV disease through maternal immunization.","authors":"Yugenia K Hong-Nguyen, Joseph Toerner, Lucia Lee, Maria C Allende, David C Kaslow","doi":"10.1038/s41541-025-01092-2","DOIUrl":"10.1038/s41541-025-01092-2","url":null,"abstract":"","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"45"},"PeriodicalIF":6.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567811","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 : 2025-03-05DOI: 10.1038/s41541-025-01094-0
Asisa Volz, Sabrina Clever, Alina Tscherne, Astrid Freudenstein, Sylvia Jany, Jan H Schwarz, Leonard Limpinsel, William G Valiant, Georgia Kalodimou, Gerd Sutter, Joseph J Mattapallil
{"title":"Efficacy of emergency maternal MVA-ZIKV vaccination in a rapid challenge model of lethal Zika infection.","authors":"Asisa Volz, Sabrina Clever, Alina Tscherne, Astrid Freudenstein, Sylvia Jany, Jan H Schwarz, Leonard Limpinsel, William G Valiant, Georgia Kalodimou, Gerd Sutter, Joseph J Mattapallil","doi":"10.1038/s41541-025-01094-0","DOIUrl":"10.1038/s41541-025-01094-0","url":null,"abstract":"<p><p>Zika virus (ZIKV) outbreak of 2015 was associated with microcephaly and congenital birth defects in children born to pregnant women infected with ZIKV. Using the highly susceptible Type I Interferon Receptor-deficient mouse-model, we demonstrate that a single emergency vaccination with a non-replicating MVA-ZIKV vaccine, when administered as early as 2-days before challenge fully protected non-pregnant and pregnant mice and fetuses against lethal ZIKV-infection. Early protection was associated with the rapid emergence of ZIKV-specific CD8+ T cell responses; depletion of CD8+ T cells resulted in the loss of protection supporting a critical role for CD8+ T cells in the early protective efficacy of MVA-ZIKV. Neutralizing antibody responses were induced later than the CD8+ T cell responses, suggesting that it may play a role in later stages of infection. Our results suggest that MVA-ZIKV induces potent anamnestic cellular immunity early after infection, contributing to its protective efficacy against rapid ZIKV challenge.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"44"},"PeriodicalIF":6.9,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11882785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143567812","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":"Optimizing rabies mRNA vaccine efficacy via RABV-G structural domain screening and heterologous prime-boost immunization.","authors":"Dongdong Li, Xuan Wang, Gaotian Li, Jingying Zhou, Lijun Bian, Xiaoyan Zhao, Liao Xing, Juanmei Zeng, Jiaxing Cui, Lili Cui, Yong Zhang, Yan Chen","doi":"10.1038/s41541-025-01098-w","DOIUrl":"10.1038/s41541-025-01098-w","url":null,"abstract":"<p><p>mRNA vaccine has become a promising technology platform for rabies prevention. This study explores the roles of different structural domains of rabies virus glycoprotein (RABV-G) and heterologous prime-boost strategies for enhanced immune responses and protection. The results suggested that mRNA vaccines encoding full-length RABV-G (RABV-Full) and RABV-R333Q induced strong immune responses and provided full protection against rabies, while mRNA vaccines encoding ectodomain/transmembrane domain (RABV-TE) and ectodomain (RABV-E) were less effective. Heterologous immunization results revealed that mRNA-primed strategies yielded higher long-lasting VNTs, but lower early VNTs than inactivated rabies virus (IRV)-primed strategies. 2×RABV-Full and IRV > RABV-Full provided 100% protection, while that of RABV-Full>IRV was 90%. Transcriptome analysis showed that rabies mRNA vaccine induced both MHCI and MHCII antigen presentation, as well as B/T cell activation. In conclusion, full-length RABV-G mRNA vaccines, particularly with an 'IRV prime and RABV-Full boost' strategy, hold great potential for rabies prevention.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"43"},"PeriodicalIF":6.9,"publicationDate":"2025-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873297/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537492","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":"Cellular immune breadth of an Omicron-specific, self-amplifying monovalent mRNA vaccine booster for COVID-19.","authors":"Durgesh Kumar, Kshitij Gaikwad, Rushank Gunnale, Sandeep Vishwakarma, Shalu Shukla, Shalini Srivastava, Janhavi Gopal, Bhalchandra Vaidya, Amit Saraf, Rohan Gurjar, Swarnendu Kaviraj, Ajay Singh, Arjun Raghuwanshi, Praveen Agarwal, Laxman Savergave, Sanjay Singh","doi":"10.1038/s41541-025-01076-2","DOIUrl":"10.1038/s41541-025-01076-2","url":null,"abstract":"<p><p>Selecting a booster vaccine strategy that generates cellular immune breadth is crucial for effectively recalling cellular reservoirs upon infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) variants. This post hoc analysis from a multicentre, randomized phase 3 study (CTRI/2022/10/046475) compared the cellular immune breadth induced by self-replicating mRNA (samRNA) vaccine GEMCOVAC-OM, encoding Omicron B.1.1.529 Spike protein, with the adenovector vaccine ChAdOx1 nCoV-19, encoding Wuhan variant Spike protein, when administered as a booster. GEMCOVAC-OM elicited significant expansion of memory B-cells (MBCs) specific to Omicron B.1.1.529, compared to ChAdOx1 nCoV-19. GEMCOVAC-OM also induced more B-cells reactive to Omicron XBB.1.5 and BA.2.86 Spike proteins. Additionally, GEMCOVAC-OM triggered higher frequencies of Omicron-Spike-specific T-cells, including stem cell, central, and effector memory subsets. In summary, while ChAdOx1 nCoV-19 showed some cross-reactivity, GEMCOVAC-OM induced a more targeted immune response. GEMCOVAC-OM offers a broader, longer-lasting immunity, making it a promising candidate for future vaccine development and global distribution.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"42"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873296/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537491","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":"Recent advances and perspectives on the development of circular RNA cancer vaccines.","authors":"Zhaohui Gong, Wentao Hu, Chengwei Zhou, Jing Guo, Lulu Yang, Boyang Wang","doi":"10.1038/s41541-025-01097-x","DOIUrl":"10.1038/s41541-025-01097-x","url":null,"abstract":"<p><p>Engineered circular RNAs (circRNAs) are emerging as promising platforms for RNA-based vaccines in cancer treatment. We summarize the recent advances of design, synthesis, and delivery of circRNA-based cancer vaccines, and highlight the applications and challenges of circRNA vaccines in cancer therapy. Further enhancements are required in areas such as antigen selection, targeted delivery, multidimensional crosstalks, and clinical trial assessments to advance the efficacy and safety of circRNA vaccines in cancer.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"41"},"PeriodicalIF":6.9,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11873252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537493","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":"SARS-CoV-2 infection primes cross-protective respiratory IgA in a MyD88- and MAVS-dependent manner.","authors":"Moe Kobayashi, Nene Kobayashi, Kyoka Deguchi, Seira Omori, Takeshi Ichinohe","doi":"10.1038/s41541-025-01095-z","DOIUrl":"10.1038/s41541-025-01095-z","url":null,"abstract":"<p><p>Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is constantly evolving mutations in the Spike protein to evade humoral immunity. Respiratory tract antiviral IgA antibodies are superior to circulating IgG antibodies in preventing SARS-CoV-2 infection. However, the role of innate immune signals required for the induction of mucosal IgA against SARS-CoV-2 infection is unknown. Here we show that hamsters recovered from ancestral SARS-CoV-2 infection are cross-protected against heterologous SARS-CoV-2 alpha, gamma, delta, and omicron BA.1 variants. Intranasal vaccination with an inactivated whole virus vaccine completely protects hamsters against heterologous SARS-CoV-2 infection. In addition, we show that intranasal boost vaccination of mice recovered from SARS-CoV-2 infection with unadjuvanted Spike protein induces robust levels of respiratory anti-Spike IgA and protects the mice from a heterologous SARS-CoV-2 infection. Furthermore, our findings suggest that MyD88 and MAVS play a role in the induction of the memory IgA response following an intranasal booster with unadjuvanted Spike protein in mice recovered from the SARS-CoV-2 infection. These findings provide a useful basis for the development of cross-protective mucosal vaccines against heterologous SARS-CoV-2 infection.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"40"},"PeriodicalIF":6.9,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11868564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524004","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":"Molecular convergence of neutralizing antibodies in human revealed by repeated rabies vaccination.","authors":"Mizuki Fujisawa, Taishi Onodera, Daisuke Kuroda, Chidchamai Kewcharoenwong, Michihito Sasaki, Yukari Itakura, Kohei Yumoto, Arnone Nithichanon, Naoto Ito, Shinji Takeoka, Tadaki Suzuki, Hirofumi Sawa, Ganjana Lertmemongkolchai, Yoshimasa Takahashi","doi":"10.1038/s41541-025-01073-5","DOIUrl":"10.1038/s41541-025-01073-5","url":null,"abstract":"<p><p>Rabies vaccines require repeated immunization to robustly elicit neutralizing antibodies that prevent fatal diseases. Here, we analyzed rabies glycoprotein antibody repertoires at both polyclonal and monoclonal levels following repeated vaccination. Booster vaccination dramatically elevated the neutralizing activity of recalled antibodies, primarily targeting an immunodominant site III epitope with hydrophilic and rugged structures. Strikingly, the majority of site III-directed antibodies in the recall response used a convergent V<sub>H</sub> gene (IGHV3-30), and they exhibited more hydrophilic and shorter paratopes than non-site III antibodies, providing physicochemical advantages for binding to site III. Additionally, several amino acids on heavy chain CDR3 were identified as key sites for acquiring an ultrapotent neutralizing activity through site III binding. Our in-depth analysis of antibody repertoires revealed the molecular signatures of neutralizing antibodies generated by repeated rabies vaccination, possibly as a result of adaptive convergence.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"39"},"PeriodicalIF":6.9,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483731","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 : 2025-02-23DOI: 10.1038/s41541-025-01082-4
Alyssa Q Stiving, Benjamin W Roose, Christopher Tubbs, Mark Haverick, Ashley Gruber, Richard R Rustandi, Jesse Kuiper, Matthew Schombs, Hillary Schuessler, Xuanwen Li
{"title":"Functionality and translation fidelity characterization of mRNA vaccines using platform based mass spectrometry detection.","authors":"Alyssa Q Stiving, Benjamin W Roose, Christopher Tubbs, Mark Haverick, Ashley Gruber, Richard R Rustandi, Jesse Kuiper, Matthew Schombs, Hillary Schuessler, Xuanwen Li","doi":"10.1038/s41541-025-01082-4","DOIUrl":"10.1038/s41541-025-01082-4","url":null,"abstract":"<p><p>The success of mRNA-based therapeutics and vaccines is attributed to their rapid development, adaptability, and scalable production. Modified ribonucleotides like N<sup>1</sup>-methylpseudouridine enhance stability and reduce immunogenicity but were recently found to induce cellular immunity to off-target, +1 ribosomal frameshifted protein. We developed a new platform using cell-free translation (CFT) and liquid chromatography-tandem mass spectrometry (MS) to detect, characterize, and quantify antigen proteins from mRNA constructs. This workflow enabled evaluation of mRNA functionality under thermal stress and assessment of multivalent formulations with high sequence homology. The MS approach was further applied following cell-based translation and demonstrated high sensitivity and specificity, accurately identifying all six translated proteins and their relative abundances from a hexavalent mRNA drug product in a dose-dependent manner. Furthermore, the CFT-MS approach successfully identified +1 ribosomal frameshifting linked to N<sup>1</sup>-methylpseudouridylation. This methodology provides a valuable analytical tool for assessing mRNA quality and functionality in vaccine development and beyond.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"38"},"PeriodicalIF":6.9,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847942/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483730","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}