NPJ Vaccines最新文献

{"title":"Lower risk of dementia with AS01-adjuvanted vaccination against shingles and respiratory syncytial virus infections.","authors":"Maxime Taquet, John A Todd, Paul J Harrison","doi":"10.1038/s41541-025-01172-3","DOIUrl":"10.1038/s41541-025-01172-3","url":null,"abstract":"<p><p>AS01-adjuvanted shingles (herpes zoster) vaccination is associated with a lower risk of dementia, but the underlying mechanisms are unclear. In propensity-score matched cohort studies with 436,788 individuals, both the AS01-adjuvanted shingles and respiratory syncytial virus (RSV) vaccines, individually or combined, were associated with reduced 18-month risk of dementia. No difference was observed between the two AS01-adjuvanted vaccines, suggesting that the AS01 adjuvant itself plays a direct role in lowering dementia risk.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"130"},"PeriodicalIF":6.9,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12198376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144497556","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 live attenuated PEDV vaccines for neonatal protection.","authors":"Wentao Li, Basav N Hangalapura, Paul van den Elzen, Erwin van den Born, Frank J M van Kuppeveld, Peter J M Rottier, Berend-Jan Bosch","doi":"10.1038/s41541-025-01195-w","DOIUrl":"10.1038/s41541-025-01195-w","url":null,"abstract":"<p><p>Porcine epidemic diarrhea virus (PEDV) causes severe diarrheal disease with high mortality in neonatal piglets. To protect suckling piglets, maternal vaccination strategies that induce lactogenic immunity in sows are crucial. To develop modified live vaccine candidates, we generated recombinant viruses with genome alterations such as deletion of the ORF3 accessory gene (ΔORF3), deletion of the N-terminal sialic acid binding domain of the spike glycoprotein (S^ΔN), and rearrangement of the spike, envelope, matrix and nucleocapsid genes (SEMN → ESMN) in the viral genome. These recombinant PEDVs were evaluated for their safety, virulence and immunogenicity in neonatal piglets. Piglets infected with the parental virus exhibited severe diarrhea and high mortality. Deletion of ORF3 alone did not attenuate the virus. Additional rearrangement of the gene order reduced virulence: rPEDV-ΔORF3-ESMN infection caused moderate diarrhea with a 50% mortality rate. The S^ΔN recombinant viruses, particularly when combined with other genome alterations, showed significantly reduced virulence, causing mild diarrhea and no mortality. These attenuated viruses retained their replicative ability in the gut and induced humoral immune responses (IgA and IgG). The rPEDV-SΔN vaccine candidate, selected for its favorable safety and immunogenicity profile, was tested in a pregnant sow vaccination and offspring challenge study for its ability to induce lactogenic immunity and confer protection to the offspring. Despite strong IgG responses, sow vaccination with rPEDV-S^ΔN resulted in low IgA serum levels and failed to protect piglets from virulent PEDV challenge. Our study defines key virulence factors for PEDV and illustrates the challenge of developing a live-attenuated vaccine that balances safety in neonatal piglets with sufficient replicative capacity in sows to stimulate lactogenic protective immunity.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"131"},"PeriodicalIF":6.9,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476145","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 centralised immunogen approach to develop a more broadly protective modified live porcine reproductive and respiratory syndrome virus 1 vaccine candidate.","authors":"Rory C F de Brito, Yashar Sadigh, Joseph Bowman, Stephanie Clive, Ben Jackson, Miriam Pedrera, Fraser Crofts, Matthieu Bernard, Fabian Z X Lean, Alejandro Núñez, Julian Seago, Jean-Pierre Frossard, Simon P Graham","doi":"10.1038/s41541-025-01192-z","DOIUrl":"10.1038/s41541-025-01192-z","url":null,"abstract":"<p><p>More efficacious vaccines are required to improve control of porcine reproductive and respiratory syndrome viruses (PRRSV). One strategy that has shown promise is the use of centralized antigens, generated from consensus sequence data. Here, we evaluated the consensus sequence approach to develop a PRRSV-1 modified live virus (MLV) vaccine candidate, 'EU-PRRSV-Con'. EU-PRRSV-Con strain was engineered by inserting consensus sequence open-reading frames encoding envelope proteins of 67 PRRSV-1 strains into an attenuated PRRSV-1 strain backbone. EU-PRRSV-Con was evaluated in pigs and benchmarked against a licensed MLV vaccine. Efficacy was assessed against three different PRRSV-1 isolates. Neutralizing antibodies were elicited by EU-PRRSV-Con, which were more reactive than those induced by the licensed MLV. EU-PRRSV-Con provided better levels of protection (reduced viral loads and lung pathology) than the licensed MLV, although the efficacy against a divergent PRRSV-1 subtype 3 strain was more limited. These data support the development of EU-PRRSV-Con as a vaccine that may aid control of PRRSV-1.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"129"},"PeriodicalIF":6.9,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340297","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":"Modeling gonorrhea vaccination to find optimal targeting strategies that balance impact with cost-effectiveness.","authors":"Trystan Leng, Lilith K Whittles, Dariya Nikitin, Peter J White","doi":"10.1038/s41541-025-01159-0","DOIUrl":"10.1038/s41541-025-01159-0","url":null,"abstract":"<p><p>Vaccination for UK men who have sex with men (MSM) at increased gonorrhea risk has been advised, but not yet implemented. Effective targeting is essential for cost-effectiveness, but previously-examined approaches have disadvantages: Vaccination-on-Diagnosis has low coverage (limiting impact), and Vaccination-according-to-Risk requires asking about sexual behavior to identify at-risk individuals, which is not always feasible. We developed a transmission-dynamic model to evaluate novel strategies offering vaccination based on information readily available to clinicians (diagnostic/vaccination history, if the patient is seeking care due to partner notification). Offering vaccination to MSM who are notified partners of gonorrhea cases or were diagnosed themselves in the past 2 years averts 1.6x more cases and is more cost-effective than Vaccination-on-Diagnosis. If vaccination provides 20% protection for 1.5 years after primary vaccination and 3 years after revaccination then at £18/dose administered, all considered strategies have ≥50 and ≥90% probabilities of positive net monetary benefit compared with no vaccination with a quality-adjusted life year valued at £20,000 and £30,000 respectively, thus meeting the UK criteria for cost-effectiveness. All novel strategies considered achieve greater impact than Vaccination-on-Diagnosis without the feasibility issues of Vaccination-according-to-Risk.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"128"},"PeriodicalIF":6.9,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12182581/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340298","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":"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}