{"title":"Concurrent infections in children with Kawasaki disease: lessons learned over 26 years.","authors":"Rakesh Kumar Pilania, Suprit Basu, Archan Sil, Sanjib Mondal, Abarna Thangaraj, Gayathri Cv, Manpreet Dhaliwal, Saniya Sharma, Ankur Kumar Jindal, Pandiarajan Vignesh, Sanjay Verma, Archana Angrup, Sanjeev H Naganur, Manphool Singhal, Amit Rawat, Deepti Suri, Surjit Singh","doi":"10.1007/s12026-025-09607-8","DOIUrl":"10.1007/s12026-025-09607-8","url":null,"abstract":"<p><p>Etiology of Kawasaki disease (KD) remains an enigma despite more than 50 years of extensive research. There is evidence that concurrent infections may play a role in the pathogenesis of KD. The present study reports various infections identified in a large cohort of patients with KD in Northwest India. We reviewed case records of patients with KD from January 1994 to February 2020. Patients with KD identified to have concurrent infection at presentation were analyzed in detail. Of 878 cases of KD during this period, 88 (60 boys, 28 girls; 64 incomplete KD, 24 complete KD) had evidence of concurrent infection. Infective manifestations included superficial and deep-seated abscesses (27.45%), pneumonia (28.4%), gastrointestinal manifestations (29.5%), urinary tract infection (4.5%), and septic arthritis (2.3%). Infectious agents were confirmed in 67/88 patients (76.13%) - these included bacteria (n = 51), viruses (n = 13), fungi (n = 2), and protozoa (n = 1). Among bacteria, infections with Staphylococcus sp. and Streptococcus sp. were the commonest (19/88 and 14/88 patients, respectively). Eighty-one children were treated with intravenous immunoglobulin (IVIg, 2 g/kg) and aspirin. Coronary artery abnormalities (CAAs) were seen in 11/88 patients (12.5%) during the acute phase - these normalized at 6 weeks of follow-up in all patients. To conclude, concurrent infections were seen in 10% of patients with KD at our center. If the clinical presentation suggests KD, one should not exclude the diagnosis even if there is evidence of an accompanying infection. Although 12.5% of patients with infection-associated KD had CAAs, none had persistent CAAs at 6 weeks of follow-up.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"56"},"PeriodicalIF":3.3,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143500759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Faris Shweikeh, Yaritza Torres, Khadeja Khan, Mohamad Mouchli, Inderprit Singh
{"title":"Hepatitis C associated mixed cryoglobulinemia glomerulonephritis in the setting of undetectable viral load: successful treatment with hydroxychloroquine and review of the literature.","authors":"Faris Shweikeh, Yaritza Torres, Khadeja Khan, Mohamad Mouchli, Inderprit Singh","doi":"10.1007/s12026-025-09608-7","DOIUrl":"10.1007/s12026-025-09608-7","url":null,"abstract":"<p><p>There are an estimated 58 million cases of Hepatitis C (HCV) worldwide. Approximately 38-76% of individuals can develop extrahepatic manifestations such as mixed cryoglobulinemia (MC). Importantly, the appearance of symptoms due to MC is linked by detectable HCV RNA. A 38-year-old male with remote history of HCV infection diagnosed 8 years prior presented to the emergency department with subacute renal failure with proteinuria, hematuria, and WBC/RBC casts. Biopsy confirmed acute proliferative, non-crescentic, inflammatory glomerulonephritis. He also had new onset cryoglobulinemia. His HCV RNA was low-grade and liver function tests were all within the normal range. A liver biopsy showed signs of chronic hepatitis with mildly active portal fibrosis. The MC was cleared with steroids and a re-measured HCV RNA quantitative was negative. Seven months later, he was readmitted with glomerulonephritis and elevated MC. However, the patient's HCV viral load was undetectable. The patient underwent 6 rounds of plasmapheresis and 6 doses of Rituximab were given with suppression of cryoglobulin to nil. A month later, the MC levels rose again, while the viral load remained undetectable with the possibility of spontaneous remission. After initiation of maintenance hydroxychloroquine, his GFR improved to normal over the next 2 years. Multiple theories have been suggested for the phenomenon including presence of residual virus and lymphoproliferation effects. Hydroxychloroquine could be a successful option, though future studies should corroborate our outcome.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"55"},"PeriodicalIF":3.3,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143467915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A case of atypical infantile de novo antiphospholipid syndrome presenting with neonatal ischemic stroke without any triggering risk factors as a \"second hit\" and review of the literature.","authors":"Doruk Bor, Mustafa Vakur Bor","doi":"10.1007/s12026-025-09605-w","DOIUrl":"10.1007/s12026-025-09605-w","url":null,"abstract":"<p><p>Infantile antiphospholipid syndrome (APS) is a rare condition arising from either transplacental transfer of antiphospholipid antibodies (aPL) from the mother or de novo antibody production in the newborn. We present a unique case of cerebral artery thrombosis with persistently elevated anti-cardiolipin and anti-β2-glycoprotein-I antibodies, despite the absence of maternal aPL, suggesting primary de novo aPL synthesis. While the prevailing \"second-hit\" hypothesis suggests that additional thrombotic risk factors are required to trigger APS in infants, our case exhibited no prenatal, maternal, or thrombophilic risk factors. A literature review of 20 reported cases further confirmed that ours was the only case without additional thrombotic triggers among the 18 cases with complete data, challenging the necessity of a \"second hit\" in neonatal APS. Notably, aPL levels normalized over time without recurrence, raising questions about the need for long-term anticoagulation in select cases, including ours. These findings suggest a potential transient form of infantile APS and highlight the importance of sequential aPL testing to guide treatment. Further research is required to elucidate the mechanisms underlying de novo aPL synthesis and its clinical implications.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"53"},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jie Guo, Chen-Guang Li, Feng-Yi Mai, Jing-Rong Liang, Ze-Hao Chen, Jiao Luo, Ming-Chao Zhou, Yu-Long Wang, Wen-Tao Yang
{"title":"Lithospermic acid targeting heat shock protein 90 attenuates LPS-induced inflammatory response via NF-кB signalling pathway in BV2 microglial cells.","authors":"Jie Guo, Chen-Guang Li, Feng-Yi Mai, Jing-Rong Liang, Ze-Hao Chen, Jiao Luo, Ming-Chao Zhou, Yu-Long Wang, Wen-Tao Yang","doi":"10.1007/s12026-025-09600-1","DOIUrl":"10.1007/s12026-025-09600-1","url":null,"abstract":"<p><p>Microglia function as a vital constituent in the maintenance of brain homeostasis. Aberrant microglial activation, however, may contribute to neurodegenerative diseases. Lithospermic acid (LA) is a plant-derived polycyclic phenolic carboxylic acid isolated from Salvia miltiorrhiza. The present study investigated the potential effects of lithospermic acid on LPS-induced neuroinflammation in BV2 microglial cells and determined the mechanism of action of this compound. Cells were pre-treated with lithospermic acid for 1 h and incubated with LPS for 24 h. qPCR, immunofluorescence, and immunoblot assays were used to determine the expression of iNOS, COX2, NF-κB p65, and HSP90 expression. ELISA was employed to measure the production of pro-inflammatory cytokines. Lithospermic acid dramatically reduced LPS-stimulated cell migration and decreased NF-κB p65 nuclear translocation. Furthermore, lithospermic acid also markedly decreased the production of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α in a dose-dependent manner. Additionally, lithospermic acid inhibited NO and PGE2 production in response to LPS, and it also inhibited the expression of iNOS and COX2 in a dose-dependent manner. Molecular docking and experimental verification have demonstrated that lithospermic acid inhibits the activity and expression of HSP90. Small interfering RNA knockdown of HSP90 expression, which abrogated LPS-induced inflammation. These findings suggest that the lithospermic acid targeting HSP90 attenuates LPS-induced inflammatory response via the NF-κB signalling pathway in BV2 microglial cells. Collectively, lithospermic acid may offer therapeutic benefits for neurodegenerative disorders associated with microglial activation and could serve as a potential inhibitor/agent for the treatment of neuroinflammation.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"54"},"PeriodicalIF":3.3,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11839720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Li Zhao, Jiangping Wu, Xiaoliang Liu, Kaiyu Zhou, Yimin Hua, Shuran Shao, Chuan Wang
{"title":"Risk factors for predicting medium-giant coronary artery aneurysms in Kawasaki disease.","authors":"Li Zhao, Jiangping Wu, Xiaoliang Liu, Kaiyu Zhou, Yimin Hua, Shuran Shao, Chuan Wang","doi":"10.1007/s12026-025-09604-x","DOIUrl":"10.1007/s12026-025-09604-x","url":null,"abstract":"<p><p>The objective of this study is to determine whether the data of blood profiles before and after therapy can be useful for predicting medium-giant coronary artery aneurysms (CAA) in patients with KD. In total, 1856 KD children from 2013 to 2022 were prospectively recruited. Serial blood samples on the day of initial IVIG infusion and 36-48 h thereafter were collected. The clinical and laboratory parameters were compared between the medium-giant CAA (n = 95) group and the non-CAA group (n = 1761). Multivariate analysis was performed to explore the independent risk factors for medium-giant CAA and the receiver operating characteristic (ROC) curve was used to evaluate and assess the prediction validities. Fever duration prior to initial IVIG infusion, IVIG resistance, cardiac enlargement, white blood cells prior to initial IVIG treatment, albumin levels, and the percentage of △neutrophils were independent risk factors for predicting medium-giant CAA. The predictive value of △neutrophil percentage (≤ 30.2%) demonstrates a relatively high sensitivity (0.84) and a moderate specificity (0.52) for predicting acute medium-giant CAA. The △neutrophil percentage before and 36-48 h after initial IVIG infusion might serve as a promising biomarker in the prediction of medium-giant CAA for KD patients.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"52"},"PeriodicalIF":3.3,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143440834","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PANoptosis-related genes in the prognosis and immune landscape of hepatocellular carcinoma.","authors":"Xiaowu Wang, Liangchen Qu, Zhikai Wen, Zhixuan Wu, Yuxiang Xue, Xuejia Yang, Ziwei Yuan, Yangyang Guo, Xingcheng Lin","doi":"10.1007/s12026-025-09603-y","DOIUrl":"10.1007/s12026-025-09603-y","url":null,"abstract":"<p><p>In hepatocellular carcinoma (HCC) individuals, the influence of numerous variables on the HCC prognosis has gained widespread recognition. Nevertheless, there remains a need for further elucidation regarding the underlying mechanism of PANoptosis-related genes (PRGs) on HCC. A consensus clustering approach, based on the TCGA-LIHC data, was used to identify specific subtypes linked to PANoptosis in this study. Next, a signature consisting of predictive differentially expressed genes for these subtypes was established using a least absolute shrinkage and selection operator (LASSO) regression analysis. Additionally, the reliability of the signature was confirmed through verification investigations using the data from the ICGC database and TCGA-LIHC. In the end, we developed a nomogram to enhance the clinical effectiveness of our prediction tool. PRG signature in this study has been highly related to the prognosis of individuals diagnosed with HCC, which was established with six genes. Also, this signature and clinicopathological features were put together to create a nomogram. Interestingly, the forecasting efficiency of this combination approach is better than other prediction models in the reported literature. In addition, an examination of the immunological surroundings indicates that the group with low risk exhibited elevated ESTIMATE score, ImmuneScores, and StromalScores. More, significant differences in infiltrating immune cells and the expression levels of immune-related genes were found between the two groups. In HCC patients, the PRG signature exhibits potential as a biomarker, offering a significant point of reference for tailoring individual therapy.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"51"},"PeriodicalIF":3.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11825605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Meysam Gachpazan, Ali Ahmadnia Alashti, Hamid Reza Jahantigh, Majid Moghbeli, Sobhan Faezi, Seyed Younes Hosseini, Mohammad Mahdi Eftekharian, Maryam Nasimi, Farhad Motavalli Khiavi, Alireza Rahimi, Reza Arabi Mianroodi, Mahdi Pakjoo, Morteza Taghizadeh, Maria Tempesta, Mehdi Mahdavi
{"title":"Immunization with recombinant HPV16-E7d in fusion with Flagellin as a cancer vaccine: Effect of antigen-adjuvant orientation on the immune response pattern.","authors":"Meysam Gachpazan, Ali Ahmadnia Alashti, Hamid Reza Jahantigh, Majid Moghbeli, Sobhan Faezi, Seyed Younes Hosseini, Mohammad Mahdi Eftekharian, Maryam Nasimi, Farhad Motavalli Khiavi, Alireza Rahimi, Reza Arabi Mianroodi, Mahdi Pakjoo, Morteza Taghizadeh, Maria Tempesta, Mehdi Mahdavi","doi":"10.1007/s12026-025-09598-6","DOIUrl":"10.1007/s12026-025-09598-6","url":null,"abstract":"<p><p>Human papillomavirus (HPV) is the leading cause of cervical cancer worldwide. The pathogenesis of HPV is mainly dependent on its E7 and E6 proteins. Up to now, different adjuvants have been used to enhance the efficacy of the immune response against these two proteins. In this study, Flagellin (FLA) was used as adjuvant to test adjuvant activity and also see whether its orientation of attachment can affect the immune response pattern. The E7d-FLA and FLA-E7d in pET28a vector were constructed and then the recombinant proteins were expressed in E. coli BL21 (DE3) bacteria under IPTG induction. The expression of recombinant E7d-FLA and FLA-E7d proteins is confirmed by SDS-PAGE and western blot. Then, recombinant fusion proteins were purified using a nickel-nitrilotriacetic acid (Ni-NTA) column. The recombinant proteins were checked for endotoxin contamination and then quantified by Bradford. Eight-to-ten-week-old male Balb/C mice were immunized subcutaneously with 10 µg recombinant E7d-FLA, FLA-E7d and HPV16E7d vaccine on days 0, 14 and 28. In addition, PBS and FLA groups were considered as control group. Then, spleen cells were harvested to assess lymphocyte proliferation and IFN-γ, IL-4 and IL-17 cytokines. In addition, mice sera were used for specific total IgG and IgG1, IgG2a, IgG2b and IgM antibodies assessment by ELISA. The results show that E7d-FLA is more potent in the induction of lymphocyte proliferation, CTL response and specific total IgG, IgG2a and IgG2b response, while the FLA-E7d vaccine was associated with more IFN-γ, and IL-17 cytokine response. The results of this study proved the ability of FLA as an adjuvant in fusion with E7d in the induction of cellular and humoral immune responses. In addition, it also emphasizes that antigen-adjuvant orientation can affect the immune response strength and polarization against HPV E7d vaccine candidate. HIGHLIGHTS: Flagellin is attached to HPV-16 E7d at the C- or N-terminus to create E7d-FLA and FLA-E7d candidate vaccines. The E7d-FLA vaccine showed a significant increase in lymphocyte proliferation, CTL response and IgG response versus FLA-E7d vaccine. The FLA-E7d vaccine is associated with a significant increase in IFN-γ and IL-17 cytokines response versus E7d-FLA vaccine. It seems that that antigen-adjuvant orientation is an important parameter in the strength and polarization of immune response in HPV E7d vaccine candidate.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"50"},"PeriodicalIF":3.3,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metformin suppresses gammadelta T17 cell differentiation alleviating DSS-induced colitis.","authors":"Mingzhong Sun, Hongli Liu, Huixiang Ju, Hongmei Chen, Rui Yang, Dongmei Yan, Langping Shen, Aiting Cai, Yaru Zhi, Lihua Xiao, Qinfang Tang, Yungang Wang","doi":"10.1007/s12026-025-09601-0","DOIUrl":"10.1007/s12026-025-09601-0","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic, nonspecific, relapsing inflammatory bowel disease. Metformin has pleiotropic effects including anti-inflammatory properties and a notable impact on the gut microbiome. γδT17 cells play crucial role in initiating and maintaining intestinal inflammation. The effect of metformin on γδT17 cells remains unclear. This study aims to explore the connection between metformin-mediated ameliorated response in colitis mice and γδT17 cell activity. The role of γδT17 cell inhibition in metformin-mediated colitis amelioration was evaluated in mice. The effect of metformin on γδT17 differentiation and the possible mechanism were evaluated in a set of in vitro experiments. Results showed that the accumulation of γδT17 cells was negatively correlated with metformin treatment in DSS-induced colitis mice. Exogenous γδT17 cells blocked metformin-mediated colitis inhibition. Furthermore, metformin inhibited γδT17 differentiation, which was related to the inhibition of mTOR/RORγt activity. Our results reveal that metformin ameliorates colitis symptoms by suppressing γδT17 differentiation, suggesting a viable strategy against UC, although the mechanism of metformin in inhibiting γδT17 differentiation remains to be further studied.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"49"},"PeriodicalIF":3.3,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11813991/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143399140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kang Xiao, Zhengyu Chen, Songqing He, Qin Long, Youxin Chen
{"title":"The role of NF-κB pathway and its regulation of inflammatory cytokines in scleral remodeling of form-deprivation mice model.","authors":"Kang Xiao, Zhengyu Chen, Songqing He, Qin Long, Youxin Chen","doi":"10.1007/s12026-025-09596-8","DOIUrl":"10.1007/s12026-025-09596-8","url":null,"abstract":"<p><p>Myopia has become a worldwide public health problem. In this study, we constructed a form deprivation (FD) myopia mouse model and explored the potential role of NF-κB pathway and inflammatory cytokines in scleral remodeling during myopia development. Wild-type (WT) mice and C6-knockout (KO) mice were categorized into two groups: FD and normal control (NC). The right eye was covered using a translucent balloon for 4 weeks, and the left eye remained untreated which served as self-control. NC group received no treatment. Refractive error and axial length were measured at baseline, 2 weeks, 4 weeks later under normal visual conditions, and 4 weeks after FD. The mRNA and protein levels of scleral TNF-α, IL-6, IL-1β, MMP-2, collagen I, and p-NF-κB p65 were detected using quantitative PCR and western blot. Under normal visual conditions, no significant difference existed in refraction and axial length between WT and C6 KO mice. After 4 weeks of deprivation, the interocular differences of C6 KO mice were lower than those of WT mice (refraction - 2.41 ± 0.86D vs. - 4.33 ± 0.87D, P = 0.003; axial length 0.044 ± 0.028 mm vs. 0.082 ± 0.026 mm, P = 0.034). Moreover, TNF-α, IL-6, IL-1β, MMP-2, and p-NF-κB p65 levels increased, and collagen I levels decreased in deprived eyes of WT mice. Whereas these trends were weakened in C6 KO mice. Scleral C5b-9 could activate the NF-κB pathway, promoting the expression of inflammatory cytokines and MMP-2 levels, which ultimately affected scleral remodeling.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"48"},"PeriodicalIF":3.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143370822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mandana Bagherzadeh, Setareh Haghighat, Mehdi Mahdavi
{"title":"Killed whole-cell Staphylococcus aureus formulation in Montanide ISA266 and Alum adjuvants: different vaccine formulations varied in the vaccine's potency and efficacy.","authors":"Mandana Bagherzadeh, Setareh Haghighat, Mehdi Mahdavi","doi":"10.1007/s12026-025-09602-z","DOIUrl":"10.1007/s12026-025-09602-z","url":null,"abstract":"<p><p>Immunotherapy can be a sensible alternative because invasive Staphylococcus aureus infection mortality, morbidity, and cost are still alarmingly high despite the development of multiple new medications to treat methicillin-resistant S. aureus infections. Herein, killed whole-cell Staphylococcus aureus was formulated in Montanide ISA266 and Alum adjuvants, and the potency and efficacy of the vaccine were studied. After the preparation of two kinds of whole-cell vaccine (bacterin and lysate), 20 µg of each vaccine candidate was formulated in Montanide ISA266 and Alum adjuvants, then subcutaneously injected in distinct groups. Blood samples were taken two weeks after each booster injection, and two booster shots were given at 2-week intervals. Sera were examined by ELISA for total IgG, isotypes (IgG1 and IgG2a), and cytokine production (IFN-γ and IL-4), respectively, to ascertain the kind of induced immune response. Experimental mice were challenged intraperitoneally with 5 × 10<sup>8</sup> CFU of bacteria 2 weeks after their last immunization, and the mortality rate and bacterial load were measured. Both immunogens elicited strong humoral immune responses, producing antibodies that improved opsonic capability, IFN-γ, and IL-4 production and protectivity in response to the experimental challenge. Compared to other immunized groups, the lysate formulation with Montanide ISA266 produced a greater antibody titer and IgG1 isotype and showed the highest vaccine potency. Additionally, combining the whole-cell vaccine (bacterin and lysate) with the adjuvant Montanide ISA266 increased IFN-γ and IL-4 cytokines response and protection in the experimental challenge. These findings show that avoiding S. aureus infection using active vaccination with inactivated whole-cell vaccines (bacterin and lysate) may be a successful strategy. The type of adjuvant in the vaccine formulation is important and influences vaccine potency and efficacy.</p>","PeriodicalId":13389,"journal":{"name":"Immunologic Research","volume":"73 1","pages":"47"},"PeriodicalIF":3.3,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143364596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}