NPJ Vaccines最新文献

{"title":"Level of antibody to hepatitis B surface antigen declined below 10 mIU/ml is still protective.","authors":"Ping Shen, Chengyu Xu, Taishun Li, Yanjing Rui, Yali Hu, Yingwei Zhang, Yi-Hua Zhou","doi":"10.1038/s41541-025-01188-9","DOIUrl":"10.1038/s41541-025-01188-9","url":null,"abstract":"<p><p>Whether declined level <10 mIU/ml of antibody to hepatitis B surface antigen (anti-HBs) is still immune to hepatitis B virus (HBV) is controversial. We longitudinally investigated hepatitis B markers in 395 vaccinated children of HBV-infected mothers at a 5.4-years interval. At baseline, they were at average age of 3.2 ± 1.8 years (0.6-12), and 106 (26.8%) children had anti-HBs <10 mIU/ml and 289 (73.2%) others had anti-HBs ≥10 mIU/ml. Of them, 84 (21.3%) were boosted with hepatitis B vaccine and 311 (78.7%) were not boosted. When they were at the age of 8.6 ± 1.9 years (6-18), 166 (42.1%) had anti-HBs <10 mIU/ml and 229 (57.9%) had anti-HBs ≥10 mIU/ml, and none was infected with HBV, including 62 unboosted children with anti-HBs <10 mIU/ml at baseline. Of 311 unboosted participants, 48 (15.4%) had increased anti-HBs levels in the absence of antibody to hepatitis B core antigen, suggesting natural booster immunization. Considering the close contact of children to their HBV-infected mothers, our study showed that successfully vaccinated children are still immune to HBV, even after the anti-HBs levels dropped to <10 mIU/ml. Therefore, anti-HBs levels <10 mIU/ml should not be an indication for booster hepatitis B vaccination.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"126"},"PeriodicalIF":6.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326367","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":"Self-assembling TLR2 agonists promote mucosal immune responses without pulmonary immunopathologic injuries in mice.","authors":"Zhangping Huang, Caiguanxi Deng, Lin Peng, Liru Shang, Juan Jiang, Wei Yu, Hao Yang, Jing Liu, Liwei Jiang, Teng Zuo, Ji Wang, Xiafeng Wang","doi":"10.1038/s41541-025-01185-y","DOIUrl":"10.1038/s41541-025-01185-y","url":null,"abstract":"<p><p>Nasal vaccines offer advantages in eliciting mucosal immunity, particularly through the induction of dimeric IgA. However, the complex mucosal environment poses challenges in achieving optimal immunogenicity and safety. This study introduced Diprovocim, a TLR2 agonist, as an effective and safe adjuvant for mucosal vaccines. Our results demonstrated that Diprovocim self-assembled into particles of suitable size for mucosal delivery, enhancing antigen phagocytosis of immune cells in both lymph nodes and lungs. After effectively activating the TLR2 signaling pathway, Diprovocim led to a reduced release of inflammatory cytokines in vivo without any tissue damage or weight loss, highlighting its safety profile. In mice, both intramuscular and intranasal immunization with Diprovocim-adjuvanted vaccines induced high titers of systemic antibodies. Higher IgG and IgA antibodies were detected in bronchoalveolar lavage fluid (BALF). Moreover, Diprovocim enhanced the immunogenicity of ovalbumin (OVA) and recombinant SARS-CoV-2 protein (RFD-Fc) vaccines, achieving higher CD4⁺ and CD8⁺ T cell immune responses and cross-protection against SARS-CoV-2 variants. These findings highlight the potential of self-assembled Diprovocim as a safe and effective adjuvant for mucosal vaccines, offering a promising strategy for combating respiratory infections.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"127"},"PeriodicalIF":6.9,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12177044/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326368","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":"Pre-clinical evaluation of a divalent liposomal vaccine to control invasive candidiasis.","authors":"Augusto Costa-Barbosa, Maria Inês Pacheco, Andreia C Gomes, Tony Collins, Manuel Vilanova, Célia Pais, Alexandra Correia, Paula Sampaio","doi":"10.1038/s41541-025-01183-0","DOIUrl":"10.1038/s41541-025-01183-0","url":null,"abstract":"<p><p>Candida albicans causes systemic infections with 20-50% mortality in critically ill and immunocompromised patients, despite antifungal treatment. Current therapies face limitations, including toxicity and resistance, underscoring the need for prophylactic vaccines. This study presents a novel divalent liposomal vaccine, delivering C. albicans Cht3 and Sap2 antigens. Vaccination induced protective Th1/Th17 immunity, a balanced Th1/Th2 ratio, antigen-specific antibodies, and boosted macrophage activity, improving survival in a mouse model of invasive candidiasis.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"124"},"PeriodicalIF":6.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166040/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294169","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":"Regulatory T cells define affinity thresholds for CD8⁺ T cell tumor infiltration.","authors":"Mona O Mohsen, Romano Josi, Sanjana V Marar, Anish Ghimire, Lan Yang, Pascal S Krenger, Arnau Solé Casaramona, Daniel E Speiser, Simone De Brot, Martin F Bachmann","doi":"10.1038/s41541-025-01177-y","DOIUrl":"10.1038/s41541-025-01177-y","url":null,"abstract":"<p><p>TCR repertoires against tumors lack high-affinity TCRs and are further suppressed by Tregs. We hypothesized that Treg depletion enhances the antitumor efficacy of low-affinity T cells. Using the weak agonistic peptide A4Y derived from LCMV glycoprotein peptide p33 as a model antigen and VLPs as a vaccine platform, we tested this approach. In a separate low-affinity model, we targeted B16F10 melanoma with our multi-target vaccine. Results revealed limited in vivo lytic cross-reactivity between A4Y and p33 peptides, and the A4Y-vaccine alone failed to inhibit B16F10p33 tumor progression. However, combining A4Y-vaccine with Treg depletion triggered a robust immune response, characterized by increased CD8+ T cell infiltration, enhanced T cell functionality, and tumor-free survival. Infiltrating T cells also exhibited closer spatial proximity and heightened migration from blood vessels. Similarly, combining low-affinity vaccine with Treg depletion enhanced antitumor responses. These findings highlight the potential of Treg depletion to advance vaccination strategies targeting TAAs with low-affinity T cells.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"125"},"PeriodicalIF":6.9,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12166054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144294170","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":"Lipid Nanoparticle Development for A Fluvid mRNA Vaccine Targeting Seasonal Influenza and SARS-CoV-2.","authors":"Jiin Felgner, Jenny E Hernandez-Davies, Erwin Strahsburger, Emily Silzel, Rie Nakajima, Aarti Jain, Jacob Laster, Jui-Lin Chiang, Yali Tsai, Philip L Felgner, D Huw Davies, Li Liang","doi":"10.1038/s41541-025-01153-6","DOIUrl":"10.1038/s41541-025-01153-6","url":null,"abstract":"<p><p>mRNA vaccines represent a promising alternative to conventional vaccines, as demonstrated by the rapid deployment of mRNA vaccines during the recent COVID-19 pandemic. In this work, we have adapted and fine-tuned various reported mRNA lipid nanoparticle (LNP) synthesis and preparation procedures, evaluated a range of ionizable cationic lipids, and identified top-performing LNP formulations. The impact of uridine modification on mRNA's ability to trigger immune responses has also been explored. Our findings indicate that both unmodified mRNA and N1-methyl pseudouridine-modified mRNA successfully induced an antigen-specific antibody response in mice, while the methoxy uridine-modified mRNA did not. Based on these studies, we constructed a bivalent Fluvid mRNA vaccine, consisting of LNPs encapsulating uridine-unmodified mRNA encoding either a transmembrane domain-deleted hemagglutinin or the full-length native spike protein. This vaccine stimulated robust T cell and B cell immune responses and conferred 100% protective efficacy against challenge with either influenza or SARS-CoV-2 viruses in the mouse model, without compromising efficacy compared to administering each monovalent vaccine individually. Our data suggest that the multivalent mRNA vaccine can offer protection against different viruses by generating humoral and cellular responses against multiple antigens at the same time.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"123"},"PeriodicalIF":6.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275484","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":"Glycoengineering of the hepatitis C virus E2 glycoprotein improves biochemical properties and enhances immunogenicity.","authors":"Liudmila Kulakova, Kiki H Li, Austin W T Chiang, Michael P Schwoerer, Saori Suzuki, Sanne Schoffelen, Khadija H Elkholy, Kinlin L Chao, Salman Shahid, Bhoj Kumar, Nathan B Murray, Stephanie Archer-Hartmann, Parastoo Azadi, Bjørn G Voldborg, Alexander Marin, Roy A Mariuzza, Alexander K Andrianov, Alexander Ploss, Nathan E Lewis, Eric A Toth, Thomas R Fuerst","doi":"10.1038/s41541-025-01161-6","DOIUrl":"10.1038/s41541-025-01161-6","url":null,"abstract":"<p><p>An effective vaccine against hepatitis C virus (HCV) must elicit the production of broadly neutralizing antibodies (bnAbs) reproducibly against the E1E2 glycoprotein complex. Little is known about how glycan content affects this process. Ideally, glycans would maximize epitope exposure without compromising antigen stability or exposing new epitopes. However, typical recombinant vaccines contain considerable heterogeneity in glycan content, which can affect the antibody response and neutralization potency. Here we employed glycoengineered Chinese hamster ovary (geCHO) cell lines that impart nearly homogeneous glycosylation as a means to test how specific glycan features influence antigenicity and immunogenicity for the secreted HCV E2 ectodomain (sE2). Specific geCHO antigens exhibited a modest but reproducible increase in affinity for some mAbs relative to CHO- and HEK293-produced sE2. Surprisingly, one geCHO sE2 antigen failed to bind the CD81 receptor, indicating the potential for significant glycan effects on biochemical properties. We immunized mice with the four antigens and found the total antibody response to be the same for all groups. However, sera from one geCHO group exhibited a 7-fold improvement in neutralization against the homologous HCV pseudovirus (HCVpp) and had the most mice whose sera exhibited neutralization activity against genotypes 1b, 2a, 2b, and 3. Further analysis identified beneficial and deleterious glycan features, and the glycan that correlated the most with decreased potency was relatively small. However, size was not the sole determinant of glycan-driven effects on the antibody response. In summary, glycan content impacts biochemical properties of antigens to varying degrees and such effects can influence immune response quality and uniformity.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"121"},"PeriodicalIF":6.9,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12159149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144275483","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":"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}

{"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}

{"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}

{"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}