ImmunoHorizons最新文献_第3页

Characterization of immune phenotypes in peripheral blood of adult renal transplant recipients using mass cytometry (CyTOF). 使用细胞计数技术（CyTOF）表征成人肾移植受者外周血免疫表型。

ImmunoHorizons Pub Date : 2025-02-18 DOI: 10.1093/immhor/vlae013

Sangeeta Kowli, Sheroy Minocherhomji, Olivia M Martinez, Stephan Busque, Herve Lebrec, Holden T Maecker

{"title":"Characterization of immune phenotypes in peripheral blood of adult renal transplant recipients using mass cytometry (CyTOF).","authors":"Sangeeta Kowli, Sheroy Minocherhomji, Olivia M Martinez, Stephan Busque, Herve Lebrec, Holden T Maecker","doi":"10.1093/immhor/vlae013","DOIUrl":"10.1093/immhor/vlae013","url":null,"abstract":"Chronic immunosuppressive therapies are crucial in organ transplantation but can increase the risk of opportunistic infections and cancer over time. We investigated immune status changes in 10 kidney transplant patients and 11 age-matched healthy adults using broad in vitro stimulation of subject-derived peripheral blood mononuclear cells followed by mass cytometry by time of flight over 6 mo. Overall, the immune cells of transplant patients exhibited increased CD8+ T cell activation and differentiation compared with healthy donors, with elevated CD8+ CD57+, MIP-1β, and interferon γ production (P < 0.05, P < 0.05, and P < 0.01, respectively). CD107a and granzyme B expression were increased in CD8+ T cells and CD56bright natural killer cells (P < 0.05 and P < 0.01, respectively), while T regulatory cells had decreased interleukin-10 production (P < 0.05). These changes indicated a proinflammatory environment influenced by induction therapy and ongoing maintenance drugs. Additionally, transplant recipients displayed signs of immune modulation, including decreased tumor necrosis factor α, interferon γ, and MIP-1β expression in γδT cells (P < 0.05 and P < 0.01), and reduced interleukin-17 and granulocyte-macrophage colony-stimulating factor expression in CD8+ T memory cell subsets (P < 0.05). The diverse functional changes underscore the importance of comprehensive immune status profiling for optimizing individual treatment strategies and developing better immunosuppressants that specifically target activated cell populations.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841977/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Biomarker expression level changes within rectal gut-associated lymphoid tissues in spinal cord-injured rats. 脊髓损伤大鼠直肠肠相关淋巴组织中生物标志物表达水平的变化。

ImmunoHorizons Pub Date : 2025-02-18 DOI: 10.1093/immhor/vlaf002

Yun Zhou, Charles H Hubscher

{"title":"Biomarker expression level changes within rectal gut-associated lymphoid tissues in spinal cord-injured rats.","authors":"Yun Zhou, Charles H Hubscher","doi":"10.1093/immhor/vlaf002","DOIUrl":"10.1093/immhor/vlaf002","url":null,"abstract":"Neurogenic bowel dysfunction (NBD) is common after spinal cord injury (SCI). Gut-associated lymphoid tissue (GALT), an organized structure within the mucosal immune system, is important for the maintenance of gut homeostasis and body health and serves as the first line barrier/defense against diet antigens, commensal microbiota, pathogens, and toxins in mucosal areas. The current study examined gene expression levels along six segments of anorectal tissue using real-time polymerase chain reaction (RT-PCR) in uninjured rats (28-day sham surgical controls) and at both 28- and 42-days post-T9 contusion injury. Consistent with our previous report of functional regional differences in the ano-rectum, we demonstrate the existence of GALTs located primarily within the segment at 3-4.5 cm from the rectal dentate line (termed rectal GALTs-rGALTs) in shams with upregulated gene expression levels of multiple biomarkers, including B cell and T cell-related genes, major histocompatibility complex (MHC) class II molecules, and germinal center (GC)-related genes, which was further confirmed by histologic examination. In the same rectal tissue segment following T9 SCI, inflammation-related genes were upregulated at 28 days post-injury (DPI) indicating that microbial infection and inflammation of rGALTs modified structure and function of rGALTs, while at 42 DPI rGALTs exhibited resolution of inflammation and impaired structure/function for extrafollicular B cell responses. Taken together, our data suggest that rGALTs exists in rat rectum for homeostasis of gut microbiota/barrier. SCI induces microbial infection and inflammation in rectal tissues containing rGALTs, which could contribute to development of SCI-related gut microbiome dysbiosis, NBD, and systemic diseases.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884801/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Regulatory T cells in the tumor microenvironment display a unique chromatin accessibility profile. 肿瘤微环境中的调节性T细胞显示出独特的染色质可及性。

ImmunoHorizons Pub Date : 2025-02-18 DOI: 10.1093/immhor/vlae014

Rebekah E Dadey, Jian Cui, Dhivyaa Rajasundaram, Hiroshi Yano, Chang Liu, Jonathan A Cohen, Andrew W Liu, Daniel H Kaplan, Creg J Workman, Dario A A Vignali

{"title":"Regulatory T cells in the tumor microenvironment display a unique chromatin accessibility profile.","authors":"Rebekah E Dadey, Jian Cui, Dhivyaa Rajasundaram, Hiroshi Yano, Chang Liu, Jonathan A Cohen, Andrew W Liu, Daniel H Kaplan, Creg J Workman, Dario A A Vignali","doi":"10.1093/immhor/vlae014","DOIUrl":"10.1093/immhor/vlae014","url":null,"abstract":"Regulatory T cells (Tregs) are a suppressive CD4+ T cell population that limit the antitumor immune response. In this study, we analyzed the chromatin accessibility of Tregs in the murine tumor microenvironment (TME) to identify tumor-specific accessible peaks and if these are altered over time in the tumor microenvironment, with or without anti-PD-1 immunotherapy. We found that despite little change in chromatin accessibility of Tregs in the tumor over time, Tregs have a distinct chromatin accessibility signature in the TME compared with Tregs in the periphery. This distinct tumor Treg chromatin accessibility profile highlights reduced accessibility at loci important for an CD4+ conventional T cell (CD4+ Foxp3-) effector phenotype. Analysis of chromatin accessibility in Tregs from B16 and MC38 tumor models indicated that Tregs from skin-resident tumors are most similar to naïve skin resident Tregs but still bear key differences attributable to the TME. We also found that Tregs do not alter their transcriptome or chromatin accessibility following immunotherapy. We conclude that although chromatin accessibility in Tregs is somewhat similar to their tissue residency, the TME may drive a unique chromatin accessibility profile. Treg chromatin accessibility in the tumor appears remarkably stable and unaltered by tumor type, over time, or following immunotherapy.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

IL-27 producers in a neonatal BCG vaccination model are a heterogenous population of myeloid cells that are diverse in phenotype and function. 新生儿卡介苗接种模型中的IL-27产生者是表型和功能各异的骨髓细胞的异质群体。

ImmunoHorizons Pub Date : 2025-02-18 DOI: 10.1093/immhor/vlaf003

Ashley M Divens, Li Ma, Jordan K Vance, Jessica M Povroznik, Gangqing Hu, Cory M Robinson

{"title":"IL-27 producers in a neonatal BCG vaccination model are a heterogenous population of myeloid cells that are diverse in phenotype and function.","authors":"Ashley M Divens, Li Ma, Jordan K Vance, Jessica M Povroznik, Gangqing Hu, Cory M Robinson","doi":"10.1093/immhor/vlaf003","DOIUrl":"10.1093/immhor/vlaf003","url":null,"abstract":"Tuberculosis (TB) is a serious public health concern in many regions of the world and the only approved vaccine to prevent TB is the live-attenuated BCG vaccine. Despite being widely used, the BCG vaccine fails to prevent pulmonary TB in adults. The BCG vaccine is administered during the neonatal period when levels of the immunosuppressive cytokine interleukin (IL)-27 are elevated, and previous studies have demonstrated that the source of IL-27 can impact downstream immune responses. We therefore sought to characterize the specific subpopulations of myeloid cells that produce IL-27 following BCG vaccination. To investigate this, we administered the BCG vaccine to neonatal IL-27p28eGFP mice that report IL-27 production. Our studies demonstrated that BCG vaccination steadily increased IL-27 production throughout the weeks post-vaccination. We also showed that a predominantly CD11b+ F4/80+ population of IL-27 producers increased MHC class II expression following BCG vaccination in both the spleen and the lung. However, producers of IL-27 in these tissues differ, with a population of CD11c+ MHC II+ cells emerging in the spleen and a subset of Ly6G/C+ MHC II+ emerging in the lung. 10x scMultiome analysis further validated the increase in MHC class II expression and demonstrated improved antigen presentation functionality following vaccination. The sequencing analysis also revealed subpopulations of IL-27 producers with immunosuppressive functions such as a population of macrophages with increased Mrc1 expression post-vaccination. Our findings suggest that IL-27 producers are a heterogenous population of myeloid cells that impact the development of protective immune responses induced by the BCG vaccine.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11884806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deficiency of H3K27 histone demethylase UTX in T cells blunts allergic sensitization and anaphylaxis to peanut. T细胞中H3K27组蛋白去甲基化酶UTX的缺乏会减弱对花生的过敏致敏和过敏反应。

ImmunoHorizons Pub Date : 2025-02-18 DOI: 10.1093/immhor/vlaf008

Robert M Immormino, Yinghui Wang, Yugen Zhang, Camille M Kapita, Kevin O Thomas, Audrey S Carson, Janelle Kesselring, Johanna Smeekens, Michael D Kulis, Timothy P Moran, Onyinye I Iweala

{"title":"Deficiency of H3K27 histone demethylase UTX in T cells blunts allergic sensitization and anaphylaxis to peanut.","authors":"Robert M Immormino, Yinghui Wang, Yugen Zhang, Camille M Kapita, Kevin O Thomas, Audrey S Carson, Janelle Kesselring, Johanna Smeekens, Michael D Kulis, Timothy P Moran, Onyinye I Iweala","doi":"10.1093/immhor/vlaf008","DOIUrl":"10.1093/immhor/vlaf008","url":null,"abstract":"Whether epigenetic factor UTX, a histone H3 lysine 27 (H3K27) demethylase, is critical for type 2 immunity, including allergic sensitization and antigen-driven anaphylaxis, is unclear. We used UTXfl/fl x Lck-Cre mice with UTX-deficient T cells (UTX-TCD) to determine whether T cell-specific UTX expression regulates antigen-specific IgE production after airway sensitization to peanut and anaphylaxis following intraperitoneal (i.p.) peanut challenge. UTX-TCD mice sensitized via the airway with peanut and lipopolysaccharide (LPS), a bacterial component and environmental adjuvant found in house dust, made 2-fold less peanut-IgE and 3.5-fold less peanut-IgG1 than comparably sensitized UTXfl/fl mice, despite higher total IgE and total IgG1 serum antibody levels pre-sensitization. Peanut-induced anaphylaxis was blunted in UTX-TCD mice, with maximum drop in core body temperature after i.p. peanut challenge two-fold lower than in UTXfl/fl mice. Compared to UTXfl/fl controls, UTX-TCD mice had reduced frequencies of CD4+ T-follicular helper (Tfh) cells and germinal center B cells, but higher frequencies of IL-4+ T-helper (Th)2, Tfh2, and IL-13+ Tfh13 cells in airway-draining mediastinal lymph nodes. UTX-TCD mice also skewed toward type 2 antibody and T-helper immune responses independent of allergic sensitization, with fewer IL-10-producing splenic Treg and T-follicular regulatory (Tfr) cells. Our results suggest that UTX expression in T cells impact the production of antigen-specific antibody responses required for allergic sensitization and antigen-specific allergic reactions, suggesting a role for H3K27 histone demethylase UTX in regulating type 2 immunity.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11893976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143598638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

What's on the horizon? 即将发生什么？

ImmunoHorizons Pub Date : 2025-01-27 DOI: 10.1093/immhor/vlaf001

Bonnie N Dittel

引用次数: 0

Improved therapeutic efficacy of a bifunctional anti-C5 mAb-FH SCR1-5 fusion protein over anti-C5 mAb in an accelerated mouse model of C3 glomerulopathy. 双功能抗c5单抗- fh SCR1-5融合蛋白比抗c5单抗在C3肾小球病变加速小鼠模型中的治疗效果更好。

ImmunoHorizons Pub Date : 2025-01-27 DOI: 10.1093/immhor/vlae006

Sayaka Sato, Takashi Miwa, Damodar Gullipalli, Madhu Golla, Eshagh Mohammadyari, Lin Zhou, Matthew Palmer, Wen-Chao Song

{"title":"Improved therapeutic efficacy of a bifunctional anti-C5 mAb-FH SCR1-5 fusion protein over anti-C5 mAb in an accelerated mouse model of C3 glomerulopathy.","authors":"Sayaka Sato, Takashi Miwa, Damodar Gullipalli, Madhu Golla, Eshagh Mohammadyari, Lin Zhou, Matthew Palmer, Wen-Chao Song","doi":"10.1093/immhor/vlae006","DOIUrl":"10.1093/immhor/vlae006","url":null,"abstract":"C3 glomerulopathy (C3G), a rare kidney disease caused by dysregulation of alternative pathway complement activation, is characterized by glomerular C3 deposition, proteinuria, crescentic glomerulonephritis, and renal failure. The anti-C5 monoclonal antibody (mAb) drug eculizumab has shown therapeutic effects in some but not all patients with C3G, and no approved therapy is currently available. Here, we developed and used a triple transgenic mouse model of fast progressing lethal C3G (FHm/mP-/-hFDKI/KI) to compare the therapeutic efficacy of a bifunctional anti-C5 mAb fused to a functional factor H (FH) fragment (short consensus repeat 1-5 [SCR1-5]) and the anti-C5 mAb itself. The new C3G mouse model is derived by humanizing factor D (hFDKI/KI) in a previously described FHm/mP-/- mouse that developed lethal C3G. We tested the effectiveness of these 2 complement inhibitors in triple transgenic mice with established C3G and glomerular disease. No FHm/mP-/-hFDKI/KI mice treated with vehicle survived the 30-d study period. All FHm/mP-/-hFDKI/KI mice treated with the C5 mAb-FH SCR1-5 fusion protein and 50% of mice treated with the anti-C5 mAb survived the 30-d treatment period. Moreover, mice treated with the C5 mAb-FH SCR1-5 fusion protein, but not those treated with the anti-C5 mAb, showed restored plasma alternative pathway complement control. The C5 mAb-FH SCR1-5 fusion protein reversed glomerular disease to a greater degree than the anti-C5 mAb. These data suggest that simultaneously inhibiting the terminal and proximal complement pathways, by anti-C5 mAb and FH SCR1-5, respectively, can reverse established C3G and is more efficacious than inhibiting the terminal pathway alone. A similar approach may be effective in treating human C3G.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841979/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antibody ligation of HLA class II induces YAP nuclear localization and formation of cytoplasmic YAP condensates in human endothelial cells. HLAⅱ类抗体连接诱导人内皮细胞YAP核定位和胞质YAP凝聚物的形成。

ImmunoHorizons Pub Date : 2025-01-27 DOI: 10.1093/immhor/vlae008

Moien Lone, Tarique Anwar, James Sinnett-Smith, Yi-Ping Jin, Elaine F Reed, Enrique Rozengurt

{"title":"Antibody ligation of HLA class II induces YAP nuclear localization and formation of cytoplasmic YAP condensates in human endothelial cells.","authors":"Moien Lone, Tarique Anwar, James Sinnett-Smith, Yi-Ping Jin, Elaine F Reed, Enrique Rozengurt","doi":"10.1093/immhor/vlae008","DOIUrl":"10.1093/immhor/vlae008","url":null,"abstract":"Antibody (Ab) crosslinking of HLA class II (HLA II) molecules on the surface of endothelial cells (ECs) triggers proliferative and prosurvival intracellular signaling, which are implicated in promoting chronic Ab-mediated rejection (cAMR). Despite the importance of cAMR in transplant medicine, the mechanisms involved remain incompletely understood. Here, we examined the regulation of yes-associated protein (YAP) nuclear cytoplasmic localization and phosphorylation in human ECs challenged with Abs that bind HLA II, which are strongly associated with cAMR. To examine changes in YAP localization in response to Ab-mediated engagement of HLA II, we used an adenoviral vector to express the class II transactivator or treatment with interferon γ. In unstimulated ECs expressing HLA II, YAP localized mainly in the cytoplasm. Stimulation with HLA II Ab (0.1-1 µg/mL) induced marked translocation of YAP to the nucleus. HLA II signaling triggered by high concentrations of HLA II Ab (1 µg/mL) also induced prominent YAP localization in cytoplasmic punctate structures that were disassembled by exposure to 1,6-hexanediol, suggesting that these structures are biomolecular condensates. Using multiple treatments, including stimulation with serum, thrombin or HLA I Ab and conditions (eg ECs plated at different densities) indicate that formation of YAP cytoplasmic puncta can be dissociated from YAP nuclear localization and phosphorylation at Ser127, a site in YAP targeted by the Hippo kinases LATS1/2. The results revealed that HLA II signaling regulates YAP subcellular distributions in ECs and demonstrate, for the first time, that HLA II Ab selectively stimulates YAP concentration in punctate structures.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841970/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143049272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Combining magnetically isolated CD45 cells with serum maintains intact drug responsiveness for ELISpot analysis in clinical trials. 在临床试验中，将磁分离的CD45细胞与血清结合可保持完整的药物反应性。

ImmunoHorizons Pub Date : 2025-01-27 DOI: 10.1093/immhor/vlae012

Chris Mavrangelos, Asiri Wijenayaka, Kurt J Sales, Patrick A Hughes

{"title":"Combining magnetically isolated CD45 cells with serum maintains intact drug responsiveness for ELISpot analysis in clinical trials.","authors":"Chris Mavrangelos, Asiri Wijenayaka, Kurt J Sales, Patrick A Hughes","doi":"10.1093/immhor/vlae012","DOIUrl":"10.1093/immhor/vlae012","url":null,"abstract":"Enzyme-linked immunosorbent spot analysis is frequently used to investigate immune responsiveness during clinical trials. However, ELISpot classically utilizes peripheral blood mononuclear cell isolates from whole blood, requiring relatively high blood draw volumes and removing both granulocytes and bound drug. Here, we describe a novel protocol whereby CD45 cells are magnetically isolated from human whole blood and co-incubated with serum isolated from the same subject. Infliximab is a well characterized anti-tumor necrosis factor α (TNF-α) antibody in clinical use since the late 1990s. We demonstrated that TNF-α inhibition by infliximab in spiked whole blood is lost on peripheral blood mononuclear cell isolation but remains in serum, and that combining serum from infliximab spiked whole blood with magnetically isolated CD45 immune cells inhibited PMA/ionomycin-stimulated TNF-α secretion. This novel protocol has important implications for enzyme-linked immunosorbent spot analysis in clinical trials in which blood volume is limited, and keeping drug responses intact provides critical information.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mixed lipopeptide-based mucosal vaccine candidate induces cross-variant immunity and protects against SARS-CoV-2 infection in hamsters. 基于脂肽的混合黏膜候选疫苗在仓鼠中诱导交叉变异免疫并保护其免受SARS-CoV-2感染。

ImmunoHorizons Pub Date : 2025-01-24 DOI: 10.1093/immhor/vlae011

Raj S Patel, Diana Duque, Jegarubee Bavananthasivam, Melissa Hewitt, Jagdeep K Sandhu, Rakesh Kumar, Anh Tran, Babita Agrawal

{"title":"Mixed lipopeptide-based mucosal vaccine candidate induces cross-variant immunity and protects against SARS-CoV-2 infection in hamsters.","authors":"Raj S Patel, Diana Duque, Jegarubee Bavananthasivam, Melissa Hewitt, Jagdeep K Sandhu, Rakesh Kumar, Anh Tran, Babita Agrawal","doi":"10.1093/immhor/vlae011","DOIUrl":"10.1093/immhor/vlae011","url":null,"abstract":"The global dissemination of SARS-CoV-2 led to a worldwide pandemic in March 2020. Even after the official downgrading of the COVID-19 pandemic, infection with SARS-CoV-2 variants continues. The rapid development and deployment of SARS-CoV-2 vaccines helped to mitigate the pandemic to a great extent. However, the current vaccines are suboptimal; they elicit incomplete and short-lived protection and are ineffective against evolving virus variants. Updating the spike antigen according to the prevailing variant and repeated boosters is not the long-term solution. We have designed a lipopeptide-based, mucosal, pan-coronavirus vaccine candidate, derived from highly conserved and/or functional regions of the SARS-CoV-2 spike, nucleocapsid, and membrane proteins. Our studies demonstrate that the designed lipopeptides (LPMix) induced both cellular and humoral (mucosal and systemic) immune responses upon intranasal immunization in mice. Furthermore, the antibodies bound to the wild-type and mutated S proteins of SARS-CoV-2 variants of concern, including Alpha, Beta, Delta and Omicron, and also led to efficient neutralization in a surrogate viral neutralization assay. Our sequence alignment and 3-dimensional molecular modeling studies demonstrated that spike-derived epitopes, P1 and P2, are sequentially and/or structurally conserved among the SARS-CoV-2 variants. The addition of a novel mucosal adjuvant, heat-killed Caulobacter crescentus, to the lipopeptide vaccine significantly bolstered mucosal antibody responses. Finally, the lipopeptide-based intranasal vaccine demonstrated significant improvement in lung pathologies in a hamster model of SARS-CoV-2 infection. These studies are fundamentally important and open new avenues in the investigation of an innovative, broadly protective intranasal vaccine platform for SARS-CoV-2 and its variants.","PeriodicalId":94037,"journal":{"name":"ImmunoHorizons","volume":"9 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11841972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143030501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0