NPJ Vaccines最新文献

{"title":"mRNA vaccines with RBD mutations have broad-spectrum activity against SARS-CoV-2 variants in mice.","authors":"Xiaoming Liang, Yuxia Yuan, Junbin Wang, Cong Tang, Yun Yang, Yanan Zhou, Hao Yang, Qing Huang, Wenhai Yu, Haixuan Wang, Yuhuan Yan, Dongdong Lin, Yanwen Li, Xuena Du, Longhai Yuan, Wenqi Quan, Daoju Wu, Shuaiyao Lu","doi":"10.1038/s41541-025-01066-4","DOIUrl":"10.1038/s41541-025-01066-4","url":null,"abstract":"<p><p>The emergence of SARS-CoV-2 variants with defined mutations that enhance pathogenicity or facilitate immune evasion has resulted in a continual decline in the protective efficacy of existing vaccines. Therefore, there is a pressing need for a vaccine capable of combating future variants. In this study, we designed new mRNA vaccines, BSCoV05 and BSCoV06, and generated point mutations in the receptor-binding domain (RBD) of the original Wuhan strain to increase their broad-spectrum antiviral activity. Additionally, we used the BA.1 RBD as a control. Both vaccines elicited a robust immune response in BALB/c and K18-hACE2 mice, generating high levels of specific binding antibodies against the BA.2 RBD. Moreover, all three vaccines induced neutralizing antibodies against the prototype viral strain and relevant variants, including the Alpha and Beta strains and the Omicron variants BA.1, BA.2, BA.5, XBB.1.5, XBB.1.16, EG.5.1, and EG.5.1.1, with BSCoV06 demonstrating broader neutralizing antibody activity. Both BSCoV05 and BSCoV06 also elicited a cellular immune response. After the challenge, both BSCoV05 and BSCOV06 provided protection against the EG.5.1 strain in both mouse strains. Therefore, these two vaccines merit further evaluation in nonhuman primates, and this vaccine design strategy should be explored for its potential application in combating future SARS-CoV-2 variants, offering valuable insights into broad-spectrum vaccine development.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"7"},"PeriodicalIF":6.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729908/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979407","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 broad spectrum Shigella vaccine based on VirG₅₃_-₃₅₃ multiepitope region produced in a cell-free system.","authors":"Girmay Desalegn, Charlotte Abrahamson, K Ross Turbyfill, Lucy Pill-Pepe, Leslie Bautista, Chitradevi S Tamilselvi, Dylan Dunn, Neeraj Kapoor, Barbara Sullinger, Matheo Herrera, Edwin V Oaks, Jeff Fairman, Marcela F Pasetti","doi":"10.1038/s41541-025-01064-6","DOIUrl":"10.1038/s41541-025-01064-6","url":null,"abstract":"<p><p>Dysentery caused by Shigella species remains a major health threat to children in low- and middle-income countries. There is no vaccine available. The most advanced candidates, i.e., O-polysaccharide (OPS)-based conjugates, have limited coverage-only against the immunizing serotype. Vaccines based on Shigella conserved proteins are sought for their simplicity and capacity to prevent disease caused by multiple serotypes. We previously reported the broad protective capacity of VirGα, a conserved surface-exposed domain of Shigella virulence factor. Seeking to refine the vaccine antigenic target and achieve scalable manufacturing compatible with Good Manufacturing Practices, we mapped linear B-cell epitopes spanning the entire VirG protein sequence by probing the immune reactivity of 10-mer peptides (overlapping 4-8 aa) with sera from Shigella-infected rhesus monkeys. The surface-exposed VirG₅₃_-₃₅₃ subregion of the passenger α-domain demonstrated the highest and strongest immunoreactivity. VirG₅₃_-₃₅₃ was produced efficiently at a large scale (>150 mg/L) using cell-free protein synthesis. When administered to mice intramuscularly, VirG₅₃_-₃₅₃ elicited robust antibody responses and conferred high levels of protection against the three most prevalent Shigella serotypes (S. flexneri 2a, 3a, and S. sonnei). VirG₅₃_-₃₅₃ evoked the production of Th2-type cytokines by spleen cells from vaccinated mice. A new universal Shigella vaccine based on VirG₅₃_-₃₅₃ meets the World Health Organization's preferred product specifications. The target antigen refinement and production improvement described here will facilitate the first-in-human studies.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"6"},"PeriodicalIF":6.9,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11731012/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979478","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":"Novel oral adjuvant to enhance cytotoxic memory like NK cell responses in HIV vaccine platform.","authors":"Mario Alles, Manuja Gunasena, Christina Isckarus, Ilmini De Silva, Sarah Board, Will Mulhern, Patrick L Collins, Thorsten Demberg, Namal P M Liyanage","doi":"10.1038/s41541-024-01053-1","DOIUrl":"10.1038/s41541-024-01053-1","url":null,"abstract":"<p><p>Natural killer (NK) cell-driven effector mechanisms, such as antibody-dependent cell-mediated cytotoxicity, emerged as a secondary correlate of protection in the RV144 HIV vaccine clinical trial, the only vaccine thus far demonstrating some efficacy in human trials. Therefore, leveraging NK cells with enhanced cytotoxic effector responses may bolster vaccine-induced protection against HIV. Here, we investigated the effect of orally administering indole-3-carbinol (I3C), an aryl hydrocarbon receptor (AHR) agonist, as an adjuvant to an RV144-like vaccine platform in a mouse model. We demonstrate the expansion of KLRG1-expressing NK cells induced by the vaccine together with I3C. This NK cell subset exhibited enhanced vaccine antigen-specific cytotoxic memory-like features. Our study underscores the potential of incorporating I3C as an oral adjuvant to HIV vaccine platforms to enhance antigen-specific cytotoxicity of NK cells against HIV-infected cells. This approach may contribute to enhancing the protective efficacy of HIV preventive vaccines against HIV acquisition.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"5"},"PeriodicalIF":6.9,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11724931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971743","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 bivalent COVID-19 mRNA vaccine elicited broad immune responses and protection against Omicron subvariants infection.","authors":"Jun Liu, Li Wang, Alexandra Kurtesi, Patrick Budylowski, Kyle G Potts, Haritha Menon, Yilin Tan, Philip Samaan, Xinan Liu, Yisen Wang, Queenie Hu, Reuben Samson, Freda Qi, Danyel Evseev, Cini John, Kristofor K Ellestad, Yue Fan, Frans Budiman, Ellaine Riczly Tohan, Suji Udayakumar, Jennifer Yang, Eric G Marcusson, Anne-Claude Gingras, Douglas J Mahoney, Mario A Ostrowski, Natalia Martin-Orozco","doi":"10.1038/s41541-025-01062-8","DOIUrl":"10.1038/s41541-025-01062-8","url":null,"abstract":"<p><p>Continuously emerging SARS-CoV-2 Omicron subvariants pose a threat thwarting the effectiveness of approved COVID-19 vaccines. Especially, the protection breadth and degree of these vaccines against antigenically distant Omicron subvariants is unclear. Here, we report the immunogenicity and efficacy of a bivalent mRNA vaccine, PTX-COVID19-M1.2 (M1.2), which encodes native spike proteins from Wuhan-Hu-1 (D614G) and Omicron BA.2.12.1, in mouse and hamster models. Both primary series and booster vaccination using M1.2 elicited potent and broad nAbs against Wuhan-Hu-1 (D614G) and some Omicron subvariants. Strong spike-specific T cell responses against Wuhan-Hu-1 and Omicron subvariants, including JN.1, were also induced. Vaccination with M1.2 protected animals from Wuhan-Hu-1 and multiple Omicron subvariants challenges. Interestingly, protection against XBB.1.5 lung infection did not correlate with nAb levels. These results indicate that M1.2 generated a broadly protective immune response against antigenically distant Omicron subvariants, and spike-specific T cells probably contributed to the breadth of the protection.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"4"},"PeriodicalIF":6.9,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952371","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":"Incremental benefit of high dose compared to standard dose influenza vaccine in reducing hospitalizations.","authors":"Shlomit Yaron, Matan Yechezkel, Dan Yamin, Talish Razi, Ilya Borochov, Erez Shmueli, Ronen Arbel, Doron Netzer","doi":"10.1038/s41541-025-01065-5","DOIUrl":"10.1038/s41541-025-01065-5","url":null,"abstract":"<p><p>Evidence regarding the high-dose (HD) vaccine's relative vaccine effectiveness (rVE) and absolute benefit in reducing influenza-related hospitalizations compared to the standard-dose (SD) vaccine is warranted. We estimated the adjusted rVE and the number needed to vaccinate (NNV) of the HD vaccine compared to the SD vaccine among Clalit Health Services members aged ≥65 years. Among 418,603 and 393,125 members vaccinated in the 2022-2023 and 2023-2024 influenza seasons, the adjusted rVE was 27% (95% CI: -12% to 61%) for 2022-2023 and 7% (95% CI: -36% to 42%) for 2023-2024, with NNV to prevent one hospitalization event being 2262 (95% CI: 1004 to ∞) and 7662 (95% CI: 1293 to ∞), respectively. Even among the highest-risk subgroup, the NNV was 1289 (95% CI: 571 to ∞) for 2022-2023 and 4719 (95% CI: 797 to ∞) for 2023-2024. The HD vaccine exhibited a limited incremental benefit, even for individuals at the highest risk.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"3"},"PeriodicalIF":6.9,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11718019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952373","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":"Development of broadly protective influenza B vaccines.","authors":"Chunyang Gu, Lavanya Babujee, David Pattinson, Shiho Chiba, Peter Jester, Tadashi Maemura, Gabriele Neumann, Yoshihiro Kawaoka","doi":"10.1038/s41541-024-01058-w","DOIUrl":"https://doi.org/10.1038/s41541-024-01058-w","url":null,"abstract":"<p><p>Influenza B viruses pose a significant threat to global public health, leading to severe respiratory infections in humans and, in some cases, death. During the last 50 years, influenza B viruses of two antigenically distinct lineages (termed 'Victoria' and 'Yamagata') have circulated in humans, necessitating two different influenza B vaccine strains. In this study, we devised a novel vaccine strategy involving reciprocal amino acid substitutions at sites where Victoria- and Yamagata-lineage viruses differ, leading to the generation of 'hybrid' vaccine viruses with the potential to protect against both lineages. Based on antigenic characterization, we selected two candidates and assessed their protective efficacy in a ferret model. Notably, both recombinant HA proteins conferred enhanced protection against heterologous challenges compared to their respective wild-type antigens. These findings show the potential of our novel strategy to develop cross-lineage protective influenza B virus vaccines.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"2"},"PeriodicalIF":6.9,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707085/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142952372","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 KIF20A-based thermosensitive hydrogel vaccine effectively potentiates immune checkpoint blockade therapy for hepatocellular carcinoma.","authors":"Xingyang Zhao, Feichao Xuan, Zirong Li, Xiangyi Yin, Xiaojun Zeng, Jiali Chen, Chihua Fang","doi":"10.1038/s41541-024-01060-2","DOIUrl":"10.1038/s41541-024-01060-2","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is a highly prevalent malignancy with limited treatment efficacy despite advances in immune checkpoint blockade (ICB) therapy. The inherently weak immune responses in HCC necessitate novel strategies to improve anti-tumor immunity and synergize with ICB therapy. Kinesin family member 20A (KIF20A) is a tumor-associated antigen (TAA) overexpressed in HCC, and it could be a promising target for vaccine development. This study confirmed KIF20A as a promising immunogenic antigen through transcriptomic mRNA sequencing analysis in the context of HCC. Therefore, we developed a thermosensitive hydrogel vaccine formulation (K/R^Lip@Gel) to optimize antigen delivery while enabling sustained in vivo release. The vaccine efficiently elicited robust immune responses by activating DCs and T cells. Moreover, K/R^Lip@Gel improved the therapeutic efficacy of PD-L1 blockade in subcutaneous and orthotopic cell-derived xenograft (CDX) models, along with immune-humanized patient-derived xenograft (PDX) HCC models, which was evidenced by improved maturation of DCs and elevated infiltration and activation of CD8⁺ T cells. These findings highlight the potential of KIF20A-based vaccines to synergistically improve ICB therapy outcomes in HCC, providing a promising approach for enhancing anti-tumor immunity and improving clinical outcomes.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"1"},"PeriodicalIF":6.9,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927540","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":"DS2 designer pre-fusion F vaccine induces strong and protective antibody response against RSV infection.","authors":"Yiling Yang, Ruoke Wang, Fenglin Guo, Tian Zhao, Yuqing Lei, Qianqian Yang, Yige Zeng, Ziqing Yang, Tatchapon Ajavavarakula, Ruijie Tan, Mingxi Li, Haodi Dong, Mengyue Niu, Keyan Bao, Hao Geng, Qining Lv, Qi Zhang, Xuanling Shi, Peng Liu, Jiwan Ge, Xinquan Wang, Linqi Zhang","doi":"10.1038/s41541-024-01059-9","DOIUrl":"10.1038/s41541-024-01059-9","url":null,"abstract":"<p><p>DS-Cav1, SC-TM, and DS2 are distinct designer pre-fusion F proteins (pre-F) of respiratory syncytial virus (RSV) developed for vaccines. However, their immunogenicity has not been directly compared. In this study, we generated three recombinant vaccines using the chimpanzee adenovirus vector AdC68 to express DS-Cav1, SC-TM, and DS2. All three vaccines elicited robust serum binding and neutralizing antibodies following intramuscular priming and boosting. DS2 induced the strongest antibody responses, followed by SC-TM and DS-Cav1. DS2 also provided strong protection against live RSV challenge. Monoclonal antibodies (mAbs) isolated from long-lived antibody-secreting cells (ASCs) in the bone marrow six months post-immunization with AdC68-DS2 predominantly targeted site Ø as well as site II. One neutralizing antibody against site II, mAb60, conferred strong protection against live RSV infection in mice. These findings highlight the strong ability of the DS2 design in eliciting long-lived antibody responses and guide the development of next-generation RSV vaccines.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"258"},"PeriodicalIF":6.9,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909887","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 the 15-valent pneumococcal conjugate vaccine, a systematic review and meta-analysis.","authors":"Gernot Wagner, Gerald Gartlehner, Kylie Thaler, Dominic Ledinger, Johanna Feyertag, Irma Klerings, K M Saif-Ur-Rahman, Declan Devane, Kate Olsson, Karam Adel Ali, Sabine Vygen-Bonnet, Heini Salo, Dace Zavadska, Marta Grgič Vitek, Marje Oona, Robert Cunney, David Tuerlinckx, Frederikke Kristensen Lomholt, Isolde Sommer","doi":"10.1038/s41541-024-01048-y","DOIUrl":"10.1038/s41541-024-01048-y","url":null,"abstract":"<p><p>Pneumococcal infections are a serious health issue associated with increased morbidity and mortality. This systematic review evaluated the efficacy, effectiveness, immunogenicity, and safety of the pneumococcal conjugate vaccine (PCV)15 compared to other pneumococcal vaccines or no vaccination in children and adults. We identified 20 randomized controlled trials (RCTs). A meta-analysis of six RCTs in infants showed that PCV15 was non-inferior compared with PCV13 for 12 shared serotypes. Based on a meta-analysis of seven RCTs in adults, PCV15 was non-inferior to PCV13 for 13 shared serotypes. For the unique PCV15 serotypes, 22F and 33F, immune responses were higher in infants and adults vaccinated with PCV15 compared to those receiving PCV13. Regarding safety, meta-analyses indicated comparable risks of adverse events between PCV15 and PCV13 in infants. Adults receiving PCV15 had a slightly higher risk of adverse events, though serious events were similar between groups.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"257"},"PeriodicalIF":6.9,"publicationDate":"2024-12-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142907358","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":"Mpox mRNA-1769 vaccine inhibits orthopoxvirus replication at intranasal, intrarectal, and cutaneous sites of inoculation.","authors":"Catherine A Cotter, Maxinne A Ignacio, Jeffrey L Americo, Patricia L Earl, Eric M Mucker, Tiffany R Frey, Andrea Carfi, Jay W Hooper, Alec W Freyn, Bernard Moss","doi":"10.1038/s41541-024-01052-2","DOIUrl":"10.1038/s41541-024-01052-2","url":null,"abstract":"<p><p>We previously reported that mice immunized twice with a lipid nanoparticle vaccine comprising four monkeypox viral mRNAs raised neutralizing antibodies and antigen-specific T cells and were protected against a lethal intranasal challenge with vaccinia virus (VACV). Here we demonstrated that the mRNA vaccine also protects mice against intranasal and intraperitoneal infections with monkeypox virus and bioluminescence imaging showed that vaccination greatly reduces or prevents VACV replication and spread from intranasal, rectal, and dermal inoculation sites. A single vaccination provided considerable protection that was enhanced by boosting for at least 4 months. Protection was related to the amount of mRNA inoculated, which correlated with neutralizing antibody levels. Furthermore, immunocompetent and immunodeficient mice lacking mature B and T cells that received serum from mRNA-immunized macaques before or after VACV challenge were protected. These findings provide insights into the mechanism and extent of mRNA vaccine-induced protection of orthopoxviruses and support clinical testing.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"9 1","pages":"256"},"PeriodicalIF":6.9,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886099","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}