NPJ Vaccines最新文献

{"title":"Validation of a multiplexed immunoassay for immunological analysis of pre erythrocytic malaria vaccines.","authors":"L K Stockdale, S Provstgaard-Morys, D Bellamy, D Woods, K Rapi, A Bajer, B Hollingdale, O Muñoz, S Malik, A V S Hill, K J Ewer","doi":"10.1038/s41541-024-01039-z","DOIUrl":"https://doi.org/10.1038/s41541-024-01039-z","url":null,"abstract":"<p><p>The primary immunological readout for clinical trials of R21/MatrixM™ malaria vaccine, is total IgG antibody specific to the central four amino acid NANP repeat region of the circumsporozoite protein. A multiplexed assay, which includes NANP, was developed and validated for four antigens representing components of the R21 immunogen. Initial assay optimisation included validation of the HBsAg international standard. Further validation performed in Oxford covered intra and inter-assay, and inter-operator variability, accuracy of QC and standard curve material, and included bridging to a singleplex NANP6 ELISA. The assay was shown to be robust and specific, with a broad dynamic range. We report a strong linear relationship between NANP6 IgG as measured by the singleplex ELISA and the multiplexed assay with rho values of 0.89 and 0.88 for two separate clinical trials (both p < 0.0005). This assay can be used to measure antibodies specific to the CSP NANP repeat region, CSP C-term region, full length R21 and HBsAg.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"14"},"PeriodicalIF":6.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TLR7/8/9 agonists and low-dose cisplatin synergistically promotes tertiary lymphatic structure formation and antitumor immunity.","authors":"Shuting Wu, Rong Xiang, Yiwei Zhong, Shushu Zhao, Zhiyu Zhang, Zhihua Kou, Shijie Zhang, Yi Zhao, Cheng Zu, Gan Zhao, Yanling Xiao, Sulin Ren, Xiaoming Gao, Bin Wang","doi":"10.1038/s41541-024-01055-z","DOIUrl":"https://doi.org/10.1038/s41541-024-01055-z","url":null,"abstract":"<p><p>In situ vaccination (ISV) triggers antitumor immune responses using the patient's own cancer antigens, yet limited neoantigen release hampers its efficacy. Our novel combination therapy involves low-dose local cisplatin followed by ISV with a TLR7/8/9 agonist formulation (CR108), in which CR108 boosts and sustains the antitumor responses induced by the cisplatin-released neoantigens. In mouse models, the cisplatin+CR108 combination significantly outperformed cisplatin or CR108 alone in abrogating established 4T1 and B16 tumors. The synergistic antitumor effects of cisplatin and CR108 were accompanied by markedly increased tumor tertiary lymphatic structures (TLS) formation, higher levels of type I and III interferons and TNF-α in serum, augmented T and B lymphocyte infiltration, antigen-presenting cell activation, as well as reduced functionally of exhausted T cells. Single-cell sequencing analysis uncovered a potential pathway for TLS to serve as a reservoir for functional antitumor effector T cells. Furthermore, cisplatin+CR108 combo therapy, but neither cisplatin nor CR108 alone, effectively inhibited the growth of treated 4T-1 tumor in an effector T cell-dependent manner. Notably, the combo therapy also suppressed the growth of distant untreated 4T-1 tumors, demonstrating systemic antitumor effects. Moreover, combo-therapy led to full regression of 4T-1 tumors in a large percentage of mice, who became strongly resistant to secondary tumor challenge, a clear indication of antitumor immunological memory. The cisplatin+CR108 combo therapy holds promise in converting \"cold\" tumors into \"hot\" ones and eliciting robust antitumor immune responses in vivo.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"13"},"PeriodicalIF":6.9,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009087","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":"HLA I immunopeptidome of synthetic long peptide pulsed human dendritic cells for therapeutic vaccine design.","authors":"Amy L Kessler, Roel F A Pieterman, Wouter A S Doff, Karel Bezstarosti, Rachid Bouzid, Kim Klarenaar, Diahann T S L Jansen, Robbie J Luijten, Jeroen A A Demmers, Sonja I Buschow","doi":"10.1038/s41541-025-01069-1","DOIUrl":"https://doi.org/10.1038/s41541-025-01069-1","url":null,"abstract":"<p><p>Synthetic long peptides (SLPs) are a promising vaccine modality that exploit dendritic cells (DC) to treat chronic infections or cancer. Currently, the design of SLPs relies on in silico prediction and multifactorial T cells assays to determine which SLPs are best cross-presented on DC human leukocyte antigen class I (HLA-I). Furthermore, it is unknown how TLR ligand-based adjuvants affect DC cross-presentation. Here, we generated a unique, high-quality immunopeptidome dataset of human DCs pulsed with 12 hepatitis B virus (HBV)-based SLPs combined with either a TLR1/2 (Amplivant®) or TLR3 (PolyI:C) ligand. The obtained immunopeptidome reflected adjuvant-induced differences, but no differences in cross-presentation of SLPs. We uncovered dominant (cross-)presentation on B-alleles, and identified 33 unique SLP-derived HLA-I peptides, several of which were not in silico predicted and some were consistently found across donors. Our work puts forward DC immunopeptidomics as a valuable tool for therapeutic vaccine design.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"12"},"PeriodicalIF":6.9,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009085","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":"Antibody responses against influenza A decline with successive years of annual influenza vaccination.","authors":"Sheena G Sullivan, Arseniy Khvorov, Louise Carolan, Leslie Dowson, A Jessica Hadiprodjo, Stephany Sánchez-Ovando, Yi Liu, Vivian K Y Leung, David Hodgson, Christopher C Blyth, Marion Macnish, Allen C Cheng, Michelle Haugenauer, Julia Clark, Sonia Dougherty, Kristine Macartney, Archana Koirala, Ameneh Khatami, Ajay Jadhav, Helen Marshall, Kathryn E Riley, Peter A B Wark, Catherine Delahunty, Kanta Subbarao, Adam J Kucharski, Annette Fox","doi":"10.1038/s41541-024-01057-x","DOIUrl":"https://doi.org/10.1038/s41541-024-01057-x","url":null,"abstract":"<p><p>Influenza vaccine effectiveness and immunogenicity can be compromised with repeated vaccination. We assessed immunological markers in a cohort of healthcare workers (HCW) from six public hospitals around Australia during 2020-2021. Sera were collected pre-vaccination and ~14 and ~180 days post-vaccination and assessed in haemagglutination inhibition assay against egg-grown vaccine and equivalent cell-grown viruses. Responses to vaccination were compared by the number of prior vaccinations. Baseline sera were available for 595 HCW in 2020 and 1031 in 2021. 5% had not been vaccinated during five years prior to enrolment and 55% had been vaccinated every year. Post-vaccination titres for all vaccine antigens were lowest among HCW vaccinated in all 5-prior years and highest among HCW with 0 or 1 prior vaccinations, even after adjustment. This was observed for both influenza A subtypes and was dependent on pre-vaccination titre. Expanded cohorts are needed to better understand how this translates to vaccine effectiveness.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"11"},"PeriodicalIF":6.9,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009084","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 synthetic cyclic peptide for promoting antigen presentation and immune activation.","authors":"Jiahui Zhang, Harrison Y R Madge, Asmaa Mahmoud, Lantian Lu, Wanyi Wang, Wenbin Huang, Prashamsa Koirala, Jazmina L Gonzalez Cruz, Wei Yang Kong, Sahra Bashiri, Ahmed O Shalash, Waleed M Hussein, Zeinab G Khalil, James W Wells, Istvan Toth, Rachel J Stephenson","doi":"10.1038/s41541-024-01050-4","DOIUrl":"10.1038/s41541-024-01050-4","url":null,"abstract":"<p><p>Cyclic peptides are often used as scaffolds for the multivalent presentation of drug molecules due to their structural stability and constrained conformation. We identified a cyclic deca-peptide incorporating lipoamino acids for delivering T helper and B cell epitopes against group A Streptococcus (GAS), eliciting robust humoral immune responses. In this study, we assessed the function-immunogenicity relationship of the multi-component vaccine candidate (referred to as VC-13) to elucidate a mechanism of action. We identified a potential universal delivery platform, not only capable of adjuvanting different peptide epitopes (e.g., NS1 and 88/30 from group A Streptococcus, gonadotropin hormone releasing hormone [GnRH]), but also protein antigens (e.g., bovine serum albumin [BSA], receptor binding domain (RBD) of the SARS-CoV-2 protein responsible for COVID-19 infection [SARS-CoV-2 RBD]) and small molecular haptens (e.g., cocaine). All vaccine candidates self-assembled into sub-500 nm nanoparticles and induced high antigen-specific systemic IgG titers and opsonic potential compared to the antigen co-administered with a commercial adjuvant, complete Freund's adjuvant. Notably, presence of the cyclic decapeptide in this vaccine increased accumulation in the draining inguinal lymph nodes, facilitating cellular uptake of peptide antigens. Furthermore, the lipoamino acid promoted dendritic cell activation, acting as both toll-like receptors 2 and 4 -targeting moiety. Our study revealed the importance of the cyclic decapeptide and lipoamino acid presence in antigen presentation and immune response activation, leading onto the development of a fully synthetic, self-assembled, and promising platform for the delivery of subunit vaccines and anti-drug vaccines.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"9"},"PeriodicalIF":6.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733015/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984349","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":"Rational selection of TbpB variants yields a bivalent vaccine with broad coverage against Neisseria gonorrhoeae.","authors":"Jamie E Fegan, Epshita A Islam, David M Curran, Dixon Ng, Natalie Y T Au, Elissa G Currie, Joseph J Zeppa, Jessica Lam, Anthony B Schryvers, Trevor F Moraes, Scott D Gray-Owen","doi":"10.1038/s41541-024-01054-0","DOIUrl":"https://doi.org/10.1038/s41541-024-01054-0","url":null,"abstract":"<p><p>Neisseria gonorrhoeae is an on-going public health problem due in part to the lack of success with efforts to develop an efficacious vaccine to prevent this sexually transmitted infection. The gonococcal transferrin binding protein B (TbpB) is an attractive candidate vaccine antigen. However, it exhibits high levels of antigenic variability, posing a significant obstacle in evoking a broadly protective immune response. Here, we utilize phylogenetic information to rationally select TbpB variants for inclusion into a gonococcal vaccine and identify two TbpB variants that together elicit a highly cross-reactive antibody response against a diverse panel of TbpB variants and clinically relevant gonococcal strains. This formulation performed well in experimental proxies of real-world usage, including eliciting bactericidal activity against diverse gonococcal strains and decreasing the median duration of colonization after vaginal infection in female mice. These data support the use of a combination of TbpB variants for a broadly protective gonococcal vaccine.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"10"},"PeriodicalIF":6.9,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11736018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143009086","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 A virus in dairy cattle: infection biology and potential mammary gland-targeted vaccines.","authors":"Rodrigo Prado Martins, Daniel Marc, Pierre Germon, Sascha Trapp, Ignacio Caballero-Posadas","doi":"10.1038/s41541-025-01063-7","DOIUrl":"10.1038/s41541-025-01063-7","url":null,"abstract":"<p><p>Influenza, a major \"One Health\" threat, has gained heightened attention following recent reports of highly pathogenic avian influenza in dairy cattle and cow-to-human transmission in the USA. This review explores general aspects of influenza A virus (IAV) biology, its interactions with mammalian hosts, and discusses the key considerations for developing vaccines to prevent or curtail IAV infection in the bovine mammary gland and its spread through milk.</p>","PeriodicalId":19335,"journal":{"name":"NPJ Vaccines","volume":"10 1","pages":"8"},"PeriodicalIF":6.9,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11730657/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979403","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":"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}