The Journal of Immunology最新文献

{"title":"Neonatal helminth infection and chronic type 2 inflammation promotes immune suppression through FcγRIIb","authors":"B. Alexander, Mindy M Miller, R. Reinhardt","doi":"10.4049/jimmunol.210.supp.82.04","DOIUrl":"https://doi.org/10.4049/jimmunol.210.supp.82.04","url":null,"abstract":"\u0000 Allergic diseases are rising in industrialized countries. This contrasts with rural communities where decreased allergic incidence correlates with increased prevalence of intestinal helminth infections. While helminths and their byproducts can ameliorate allergic inflammation in adult mice with established disease, it remains unknown if early-life exposure can prevent or delay allergic disease onset. We utilized a neonatal infection model with the gastrointestinal helminth Heligmosomoides polygyrusand found that neonatal H. polygyruscolonization results in chronic infection and type 2 inflammation. This study investigates how chronic and systemic type 2 hallmarks IL-4 and IgG1 may be involved in the long-term suppressive mechanisms induced by neonatal helminth colonization. We hypothesize that IL-4-induced upregulation of the sole inhibitory Fc receptor, FcγRIIb, allows for sustained suppression of T cell mediated inflammation by increasing the activation threshold of antigen presenting cells. Increasing this threshold prevents allergen-specific T cells from becoming optimally activated and instead promotes T cell tolerance. In addition to IL-4 increasing expression of FcγRIIb on macrophages, it promotes the production of its ligand IgG1, completing the suppressive circuit. This model predicts that elimination of FcγRIIb and/or IL-4 will result in greater T cell activation and allergic inflammation. Our in vivoand in vitrodata show that FcγRIIb is necessary for reducing allergic airway inflammation and T cell activation after allergen challenge. Taken together, these data support a model in which chronic helminth infection naturally mimics the suppressive effects of intravenous immunoglobulin therapy.\u0000 Supported by the National Institutes of Health NIAID training grant (Training Program in Immunology; T32-AI07405)","PeriodicalId":22698,"journal":{"name":"The Journal of Immunology","volume":"68 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78736857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergy between oxaliplatin and adenovirus initiates immunogenic cell death in human colorectal carcinoma cells","authors":"J. Jessup, S. Hewitt, T. Fuerst","doi":"10.4049/jimmunol.210.supp.145.19","DOIUrl":"https://doi.org/10.4049/jimmunol.210.supp.145.19","url":null,"abstract":"\u0000 Externalization of Calreticulin (CALR) is the critical first step in the initiation of Immunogenic Cell Death. Since Oxaliplatin (OX) cooperates with an oncolytic chimeric human adenovirus Ad5/3-NP2.ADP (ADP) to induce adaptive immunity as well as regression of established cancer, we sought to determine whether the cooperation was additive or synergistic. Methods include immunohistochemistry (IHC) for Calreticulin expression in mice 11 days after intratumoral injection of the OX-ADP mixture. In vitro assays with limiting dilutions of OX and ADP on human Clone A colorectal carcinoma cell monolayers were cultured for 3 days and cytotoxicity, viral infectivity by GFP, and the expression of externalized CALR (ectoCALR) on Clone A cells measured by static cytometry. Synergy was measured using SynergyFinder 3.0 (Ianevski et al., PMC9252834) that creates 2-D interactive surfaces to measure synergy and antagonism. Areas of synergy have mean scores > 10. IHC revealed strong CALR expression in OX-ADP treated tumors, weak expression in tumors injected with OX or ADP alone and minimal in PBS treated controls. Mean Viral Infectivity synergy score was 27.2 for the area of (Ox μM, ADP MOI): (0.12μM, 4 MOI) to (12.5μM, 100 MOI) while mean synergy score for ectoCALR expression was 29.2 for OX/ADP (0.01μM, 0.16) to (0.12μM, 20 MOI). The role of oxidative and endoplasmic reticulum stress as the basis of synergy is under study. Oxaliplatin and adenovirus are synergistic in their ability to initiate ICD which is important for vaccine development.","PeriodicalId":22698,"journal":{"name":"The Journal of Immunology","volume":"24 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78807975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"c-Kit signaling modulated group 3 innate lymphoid cell functions in mouse neutrophilic asthma model","authors":"Jheng-Syuan Shao, Po-Yu Chi, Yajie Chang","doi":"10.4049/jimmunol.210.supp.67.08","DOIUrl":"https://doi.org/10.4049/jimmunol.210.supp.67.08","url":null,"abstract":"\u0000 Group 3 innate lymphoid cells (ILC3s) are involved in air pollution- and bacterial infection-associated neutrophilic asthma. Studies showed that asthmatic patients have higher stem cell factor (SCF) expression in airway and sera. Of note, ILC3s express SCF receptor, c-Kit, suggesting a potential role of SCF/c-Kit signaling in ILC3 functions and neutrophilic asthma. In this study, we aimed to determine whether SCF/c-Kit signaling could modulate ILC3 functions and neutrophilic asthma. Wild-type (WT) and c-Kit deficient mice (Kit w-sh) were intranasally treated with IL-1β/IL-23 or particulate matter (PM) 2.5 to induce neutrophilic asthma. While IL-1β/IL-23 or PM2.5 caused increases in neutrophil infiltration to bronchoalveolar lavage fluid (BALF) and airway hyperreactivity (AHR) in WT mice, Kit w-shmice had decreased infiltration of neutrophils and ameliorated AHR. Concomitantly, flow cytometry results showed a decreased number of IL-17+ ILC3 in the lung of Kit w-shmice compared to WT mice, which may be due to the reduced proliferation of c-Kit-deficient ILC3. In addition, we showed SCF enhanced IL-17 secretion from ILC3s in vitro. Based on re-analysis of published mouse whole lung cells scRNAseq data, we hypothesized fibroblasts are the source of SCF. Indeed, mice with SCF knockout in fibroblast exhibited decreased neutrophil infiltration and reduced IL-17+ ILC3 number in response to IL-1β/IL-23. Finally, administration of imatinib, a FDA-approved drug targeting c-Kit signaling, ameliorated AHR and ILC3 activation in the mouse neutrophilic asthma model. Taken together, our data suggested that inhibition of ILC3 activation by targeting c-Kit signaling may provide a potential therapeutic management for neutrophilic asthma.","PeriodicalId":22698,"journal":{"name":"The Journal of Immunology","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78853483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Programming of checkpoint blockade responsive exhausted T cells by rheostatic IL-2 signals during priming by dendritic cells","authors":"S. Sarkar, R. Toumi, Hanxi Xiao, T. Pulliam, J. Reed, P. Nghiem, V. Kalia","doi":"10.4049/jimmunol.210.supp.83.16","DOIUrl":"https://doi.org/10.4049/jimmunol.210.supp.83.16","url":null,"abstract":"\u0000 Stem-like progenitor exhausted CD8 T cells are critical for maintaining long-term resistance during chronic infections and cancer, and represent an important checkpoint blockade immunotherapy target for functional reinvigoration and disease control. Here, we show a fate-deterministic role of rheostatic IL-2 signals and differential DC priming in programming the development of stem-like progenitor exhausted CD8 T cells during chronic viral infection. In vivo fate-tracking studies reveal that strong IL-2 signals during priming drive terminal differentiation. In contrast, tempered IL-2 signals are associated with TCF-1 Histem-like precursors, which give rise to progenitor exhausted CD8 T cells, capable of long-term persistence and potent responsiveness to anti-PD-1 therapy in later stages of chronic viral infection. In the context of human tumors as well, single cell RNA-seq analyses of total or antigen-specific tumor infiltrating lymphocytes show an inverse relationship of IL-2 signaling signature with T cell stemness, as well as checkpoint blockade therapy outcomes in melanoma. Our studies further show that the rheostatic control of exhausted T cell fates by differential IL-2 signals is physiologically mediated through differential cell surface expression of IL-2Rα during early stages of T cell activation, which in turn is pioneered during priming by distinct dendritic cell subsets. Notably, moderation of in vivo IL-2 signals during priming promotes the development of stem-like TCF-1 Hilineage, thus supporting a unique strategy for improving clinical immunotherapy outcomes by enhancing the development of long-lived, therapy-responsive stem-like cells with vigorous effector expansion capabilities.\u0000 Pediatric Cancer Research Foundation to SS, the Rachel Lynn Henley Foundation to VK, the Hopes and Smiles For Children Foundation to VK, In Concert for Cancer Foundation to VK and the National Institutes of Health (CA254168 to TP; CA225517 to PN; AI132819, AI103748 to SS; 5P30CA015704; AI154363 to VK)","PeriodicalId":22698,"journal":{"name":"The Journal of Immunology","volume":"99 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78375851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intramuscular mRNA prime plus intranasal adenoviral vector booster elicit robust respiratory mucosal IgA responses against SARS-CoV-2","authors":"Jinyi Tang, Yue Wu, C. Zeng, Justin J. Taylor, Guizhi Zhu, D. Weissman, Shan-Lu Liu, Jie Sun","doi":"10.4049/jimmunol.210.supp.253.14","DOIUrl":"https://doi.org/10.4049/jimmunol.210.supp.253.14","url":null,"abstract":"\u0000 Current SARS-CoV-2 mRNA vaccines induce robust humoral and cellular immunity in the circulation, but its ability in eliciting respiratory mucosal immunity is less characterized. Here, we demonstrated that systemic mRNA expressing ancestral spike (mRNA-S) vaccination alone induced weak respiratory mucosal neutralizing antibody and cellular immunity, particularly against SARS-CoV-2 Omicron strain. In contrast, an immunization strategy combining systemic mRNA-S administration plus mucosal adenoviral vector expressing ancestral spike (Ad5-S) booster induced strong T cell, B cell, and antibody responses in the respiratory tract, which can last for a long time. Furthermore, we found that Ad5-S mucosal booster promoted robust IgA-producing B cells in the respiratory tract, which were correlated with the levels of mucosal S-specific IgA levels. Strikingly, these local IgA-producing B cells were more cross-reactive to the Delta and Omicron Spike proteins compared to those IgG-producing B cells. We further showed that CD4 T cell help was required for the development of IgA-producing B cell in the respiratory mucosa. Taken together, our study identified a vaccination strategy and its associated mechanisms for the induction of strong cross-reactive IgA responses, which were shown to correlate with optimal protection against breakthrough infection, especially by Omicron sub-lineages. Hence, our data provide insights into the rational design of next-generation SARS-CoV-2 mucosal vaccines required for the protection against infection by SARS-CoV-2 Omicron sub-lineages or future variants.","PeriodicalId":22698,"journal":{"name":"The Journal of Immunology","volume":"121 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78433867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor infiltrating natural killer cells in soft tissue sarcoma are predominantly CD56 dim: Implications for outcomes","authors":"Cyrus J. Sholevar, Sylvia M Cruz, Khurshid R. Iranpur, S. Judge, Alicia A. Gingrich, Lauren E Farley, Aryana M. Razmara, M. Lammers, S. Thorpe, A. Monjazeb, W. Murphy, R. Canter","doi":"10.4049/jimmunol.210.supp.237.07","DOIUrl":"https://doi.org/10.4049/jimmunol.210.supp.237.07","url":null,"abstract":"\u0000 Natural killer (NK) cells have been shown to be important mediators of anti-tumor responses, including in soft tissue sarcomas (STS). NK cells show significant heterogeneity, depending on maturation, tissue residency, and inflammatory environment. As previous studies have suggested that tumor-infiltrating NK cells (TiNKs) acquire a less cytotoxic CD56 brighttissue resident phenotype, we sought to compare blood versus tumor NK cell phenotype in STS and evaluate any association with survival. Blood and tumor from 27 STS patients undergoing surgery from 2018–2022 were collected prospectively for flow cytometry and retrospectively analyzed. 52% were female, the mean age was 59, and 74% were AJCC stage 3. Increasing absolute number of NK cells in the blood correlated with longer survival (P<0.005, r=0.6). As expected, CD56 dimNK cells predominated in the blood (91.5±5.8% of CD3-CD56+ lymphocytes compared to 80.1±13% in tumor, P<0.005). In contrast, CD56 brightcells were enriched in tumor representing 18.5±13% compared to 8.4±5.8% in blood (P<0.005). Although CD56 brightNK cells were approximately 2.4±3-fold higher in tumor compared to blood, CD56 dimNK cells still represented the majority of TiNKs. Higher proportions of both overall NK cells and CD56 dimNK cells in STS tumors were associated with better metastasis-free survival on Kaplan-Meier analysis (P<0.05). CD56 dimTiNKs had higher NKp46 expression than CD56 brights. In conclusion, both blood and intra-tumoral NK cells appear prognostic in STS. Although the proportion of CD56 brightTiNKs in STS is higher than blood the majority of TiNKs are CD56 dimconsistent with a cytotoxic phenotype. Better characterization of NK subsets in STS is likely to have translational significance.","PeriodicalId":22698,"journal":{"name":"The Journal of Immunology","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75890732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Does the upper respiratory tract microbiome change in dairy calves fed milk replacer containing probiotics?","authors":"C. Chitko-McKown, T. McDaneld, J. Kritchevsky, K. A. Bryan, S. Eicher","doi":"10.4049/jimmunol.210.supp.225.01","DOIUrl":"https://doi.org/10.4049/jimmunol.210.supp.225.01","url":null,"abstract":"\u0000 Our overall hypothesis is that feeding probiotics to dairy calves will alter overall immunity and may additionally change the microbiome in the respiratory tract as well as the gut. A group of 20 dairy calves were split into two treatment groups: Control (N=10, milk replacer), and Probiotic (N=10, milk replacer + 0.5 g/day Bovamine Dairy). On day 0 birth weight was obtained and the calves were provided colostrum as per the dairy SOP. On day 2, probiotics were added to the milk replacer of the treated group. Blood was collected along with nasal and tonsil swabs on days 0, 7, 14, 21, 28, 42, and 48. Calves were monitored daily for fecal, nasal, and ocular discharge scores. Our preliminary data showed no significant differences (P<0.5) between the Control and Probiotic groups in immune cell populations in peripheral blood. DNA was extracted from nasal and tonsil swabs to evaluate the bacterial populations in the upper respiratory microbiome. Hypervariable regions 1 through 3 along the 16S ribosomal RNA gene were amplified by PCR and sequenced by Illumina MiSeq to determine the bacterial taxa present. Evaluation of these samples revealed a greater percentage of operational taxonomy units (OTU) were classified at the genus level in the tonsil compared to the nasal samples. The microbiome of the tonsils was more stable over time points compared to the nasal samples. Evaluation of each timepoint for nasal and tonsil samples identified bacterial taxa that changed in relative abundance with the addition of the probiotic compared to the control diet. Addition of probiotic changed the relative abundance of OTU (P<0.01) in the nasal and tonsil sampling sites and at multiple timepoints. Analyses are ongoing.\u0000 Project supported by fund from the USDA Agricultural Research Service.","PeriodicalId":22698,"journal":{"name":"The Journal of Immunology","volume":"53 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75953367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CpG therapeutic efficacy in a murine model of metastatic Lymphangioleiomyomatosis (LAM) is mediated by plasmacytoid dendritic cell and T cell immune responses","authors":"M. Amosu, Jacob McCright, Kaitlyn Moore, K. Maisel","doi":"10.4049/jimmunol.210.supp.226.19","DOIUrl":"https://doi.org/10.4049/jimmunol.210.supp.226.19","url":null,"abstract":"\u0000 \u0000 \u0000 LAM is a slow growing, metastasizing neoplasm affecting women of reproductive age, marked by abnormal growth of smooth muscle-like cells leading to cystic lung destruction. LAM has hallmarks of cancer, like expression of immune checkpoint receptors. Effective cancer therapies promote robust T cell responses through activated dendritic cells (DCs). Anti-cancer strategies, like toll like receptor (TLR) activation and immune checkpoint inhibition could work as LAM therapy. In this study, we examine the effect of CpG, a TLR9 agonist, on the DC and T cell responses in murine LAM.\u0000 \u0000 \u0000 \u0000 We used a mouse model of metastatic LAM to determine survival after biweekly intranasal CpG therapy (10μg/ 5μg) with/ without systemic α-PD-1, rapamycin, or α-CD317 therapy. We used ELISA to measure the cytokine profile and flow cytometry to quantify cell populations between CpG-treated and untreated LAM lungs.\u0000 \u0000 \u0000 \u0000 We found that CpG treatment enhances median survival from 32 to 60 days in murine LAM (p <0.0001). Efficacy of CpG treatment in LAM is facilitated by plasmacytoid DCs. pDC depletion in CpG-treated mice decreases survival from 60 to 52 days (p=0.028). CpG-treated LAM lungs also produce more IFN-α (p=0.031). CpG-treated LAM lungs have increased IFN-γ (p= 0.012) and IL-12 (p= 0.005), cytokines secreted by cytotoxic T cells. CpG-treatment is synergistic with α-PD-1 checkpoint inhibition (p=0.004) and can be administered with rapamycin without adverse effects on median survival.\u0000 \u0000 \u0000 \u0000 In LAM, CpG therapy is mediated by pDC dependent immune responses and cytotoxic T cells. This suggests that adjuvant immunotherapy, like CpG, may offer new treatment options for LAM compatible with the current standard of care, rapamycin.\u0000 \u0000 \u0000 \u0000 The LAM Foundation Research Grant Award\u0000","PeriodicalId":22698,"journal":{"name":"The Journal of Immunology","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75050465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-Intrinsic Effects of TGF-b Signaling in Mast Cell Effector Function that Modulate Allergic Inflammation","authors":"T. Haque, Leshawna Leak, K. Laky, Pamela Guererrio","doi":"10.4049/jimmunol.210.supp.151.05","DOIUrl":"https://doi.org/10.4049/jimmunol.210.supp.151.05","url":null,"abstract":"\u0000 IgE mediated mast cell activation is a key feature of allergic disease, although the mechanisms that govern mast cell homeostasis are not fully understood. The TGFb signaling pathway has been shown to regulate mast cell effector function. Furthermore, variants in the TGFb signaling pathway are associated with allergic diseases; TGFb mediated mast cell regulation is likely involved in the allergy diathesis. Patients with Loeys Dietz Syndrome (LDS), a disorder caused by loss of function variants in TGFBR1and TGFBR2, are predisposed to develop allergic diseases, thus provide an opportunity to study the role of mast cell TGFb signaling in allergic diseases. Mast cells are activated through the high affinity IgE receptor FcERI causing the release of granules containing mediators that are directly involved in anaphylaxis and other allergic symptoms. IgE mediated activation can be modulated by other co-stimulatory signals such as the type 2 alarmin IL-33. We examined murine mast cells carrying an LDS mutation, or with conditional deletion of Tgfbr1, and found that they degranulated less in response to IgE/antigen, in vivo and in vitro. This phenotype was not tied to changes in the IgE and SCF receptor expression or mast cell tissue distribution in mice and was recapitulated in human LDS mast cells, in vitro. Additionally, LDS mice responded more to IL-33 stimulation. Mechanistically, the LDS anaphylaxis phenotype was linked to IL-33, as the reduction of anaphylaxis in LDS mice was partially restored in IL-33RKO LDS mice. Thus, the TGFb-IL-33R axis likely plays a major role in controlling IgE mediated mast cell functions. Taken together, TGFb signaling upregulates mast cell effector function by disrupting an IL-33/ST2 mediated regulatory pathway.\u0000 Intramural NIAID Support","PeriodicalId":22698,"journal":{"name":"The Journal of Immunology","volume":"70 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72657377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved control of SARS-CoV-2 infection with nucleocapsid-specific antibodies","authors":"P. Penaloza-MacMaster, Tanushree Dangi, Sarah Sanchez, Jacob Class, M. Richner, L. Visvabharathy, Young Rock Chung, Kirsten Bentley, R. Stanton, I. Koralnik, Justin M. Richner, P. Penaloza-MacMaster","doi":"10.4049/jimmunol.210.supp.235.26","DOIUrl":"https://doi.org/10.4049/jimmunol.210.supp.235.26","url":null,"abstract":"\u0000 The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein is the main antigen in all approved COVID-19 vaccines and is also the only target for monoclonal antibody (mAb) therapies. Immune responses to other viral antigens are generated after SARS-CoV-2 infection, but their contribution to the antiviral response remains unclear. Here, we interrogated whether nucleocapsid-specific antibodies can improve protection against SARS-CoV-2. We first immunized mice with a nucleocapsid-based vaccine and then transferred sera from these mice into naive mice, followed by challenge with SARS-CoV-2. We show that mice that received nucleocapsid-specific sera or a nucleocapsid-specific mAb exhibited enhanced control of SARS-CoV-2. Nucleocapsid-specific antibodies elicited NK-mediated, antibody-dependent cellular cytotoxicity (ADCC) against infected cells. To our knowledge, these findings provide the first demonstration in the coronavirus literature that antibody responses specific to the nucleocapsid protein can improve viral clearance, providing a rationale for the clinical evaluation of nucleocapsid-based mAb therapies to treat COVID-19.\u0000 NIH (DP2DA051912)","PeriodicalId":22698,"journal":{"name":"The Journal of Immunology","volume":"215 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72665096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}