Journal of AIDS and immune research最新文献

CAR T Cell-Packaged Oncolytic Vaccinia Virus Displays Enhanced Antitumor Efficacy CAR - T细胞包装的溶瘤痘苗病毒显示增强的抗肿瘤效果

Journal of AIDS and immune research Pub Date : 2021-09-10 DOI: 10.26420/jimmunres.2021.1041

Kevin Song, Xing-bing Wang

{"title":"CAR T Cell-Packaged Oncolytic Vaccinia Virus Displays Enhanced Antitumor Efficacy","authors":"Kevin Song, Xing-bing Wang","doi":"10.26420/jimmunres.2021.1041","DOIUrl":"https://doi.org/10.26420/jimmunres.2021.1041","url":null,"abstract":"Background: Oncolytic vaccinia virus is a promising cancer therapeutic modality. However, the effectiveness of oncolytic viruses is limited by several factors. Systemic or intratumoral delivery of vaccinia viruses with the subsequent quick clearance of the viruses from the tumor site and the body by the strong immune responses induced by the virus are among the key challenges. In this study, we explored CAR T cell-packaged oncolytic vaccinia virus as a combinational therapy strategy in order to overcome current limitations for oncolytic virotherapy. Materials and Methods: We generated human HER2-CAR T cells and infected the HER2-CAR T cells with a EphA2-CD3 T cell engager-armed oncolytic vaccinia virus and evaluated the virus infectivity and replication within the T cells by flow analysis and virus tittering. T cell activation and cytotoxicity were determined by ELISA and 51Cr release assay. Results: We demonstrated that oncolytic vaccinia virus infected human HER2-CAR T cells effectively and virus particle in the activated human T cells increased >1000 fold in 3 days. In addition, EphA2-CD3 T cell engager effectively activated HER2-CAR T cells in the presence of HER2dimEphA2high NSCLC A549 cell lines, indicated by the elevated expression level of IFNγ and IL2. Importantly, in vitro studies showed that HER2-CAR T cell-packaged EphA2-TEA-VV displayed enhanced cytotoxicity against HER2dimEphA2high NSCLC A549 cell lines compared to HER2-CAR T cells or EphA2-TEA-VV alone. Conclusion: HER2-CAR T cell-packaged EphA2-TEA-VV is a promising therapeutic candidate with the ability to overcome the virus’s high immunogenicity and tumor heterogeneity, resulting in enhanced antitumor effects.","PeriodicalId":91526,"journal":{"name":"Journal of AIDS and immune research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84818429","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}

引用次数: 0

Clinical Performance of Two Methods for Detecting Anti SARS-CoV-2 Antibodies 两种抗SARS-CoV-2抗体检测方法的临床性能

Journal of AIDS and immune research Pub Date : 2021-05-27 DOI: 10.26420/jimmunres.2021.1040

D. Jacobsen, D. Gonzalez, J. Jamardo, B. Perazzi, Repetto Em, B. Fabre, C. Ibar, L. Pugliese, F. Fortuna, E. Carrizo, Caro Em, G. Reboredo, Argentina Coordinadora de Salud Misionar, Argentina Biogenar Laboratorio

{"title":"Clinical Performance of Two Methods for Detecting Anti SARS-CoV-2 Antibodies","authors":"D. Jacobsen, D. Gonzalez, J. Jamardo, B. Perazzi, Repetto Em, B. Fabre, C. Ibar, L. Pugliese, F. Fortuna, E. Carrizo, Caro Em, G. Reboredo, Argentina Coordinadora de Salud Misionar, Argentina Biogenar Laboratorio","doi":"10.26420/jimmunres.2021.1040","DOIUrl":"https://doi.org/10.26420/jimmunres.2021.1040","url":null,"abstract":"Evaluating the clinical performance of available methods to detect antibodies against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has become a primordial issue in clinical laboratories. The aim of this study was to evaluate the clinical performance of two methods for SARS-CoV-2 antibodies detection, an automated Chemiluminescent Immunoassay (CLIA) and an immunochromatographic Lateral-Flow Assay (LFA) in patients with positive reverse transcription polymerase chain reaction (RT-PCR). Performance for CLIA method was Positive Agreement (PA) 56.6% and Negative Agreement (NA) 96,6% for IgM and PA 85.8%/NA 90,2% for IgG. Performance for LFA method was PA 56.2% and NA 100% for IgM and PA 95.5% and NA 100 % for IgG. LFA general agreement IgG was better than CLIA. In both methods, significant differences in Kappa index are observed when IgG and IgM are compared. When evaluating the data from a clinical perspective, we found that both method performance for IgM detection may not meet the expected requirements for their clinical utility and could lead to an inappropriate medical decision. The findings of this study show that both immunoassay methods might be reliable for assessing immunological response in COVID-19 patients. Our results also confirm that IgG measurement could be helpful, especially for epidemiological studies in our population. These results provide evidence to justify epidemiological studies in our population.","PeriodicalId":91526,"journal":{"name":"Journal of AIDS and immune research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81643766","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}

引用次数: 0

The Pivotal Role of Signal Regulatory Protein α in Exacerbating Pulmonary Fibrosis Complicated with Bacterial Infection 信号调节蛋白α在加重肺纤维化并发细菌感染中的关键作用

Journal of AIDS and immune research Pub Date : 2021-05-11 DOI: 10.26420/jimmunres.2021.1039

R. Yamaguchi, A. Sakamoto, M. Haraguchi, S. Narahara, H. Sugiuchi, Y. Yamaguchi

{"title":"The Pivotal Role of Signal Regulatory Protein α in Exacerbating Pulmonary Fibrosis Complicated with Bacterial Infection","authors":"R. Yamaguchi, A. Sakamoto, M. Haraguchi, S. Narahara, H. Sugiuchi, Y. Yamaguchi","doi":"10.26420/jimmunres.2021.1039","DOIUrl":"https://doi.org/10.26420/jimmunres.2021.1039","url":null,"abstract":"The pathogenesis of pulmonary fibrosis remains unknown. However, bacterial infections in patients with idiopathic pulmonary fibrosis are a serious complication that exacerbate the disease. Serum levels of Surfactant Protein D (SPD) are known to be elevated in patients with pulmonary fibrosis, but the role of SPD in pulmonary fibrosis complicated with bacterial infection is unknown. Lipopolysaccharide upregulates Interleukin (IL)-12p40 expression and IL-12p40 promotes Interferon Gamma (IFNγ) production to induce the T helper cell 1 (Th1) immune response via Signal Transducers and Activators of Transcription 4 (STAT4) signaling. A lack of IFNγ shifts the immune response from Th1 to Th2. IL-4 is a profibrotic Th2 cytokine that activates fibroblasts. Granulocyte-macrophage colony-stimulating factor induced by IL-1 and TNFα during the Th1 immune response upregulates Signal Regulatory Protein α (SIRPα) expression. Interferon Regulatory Factor 1 (IRF1) functions as the promoter activator of IL-12p40 after stimulation with LPS. SPD is a ligand for SIRPα, and SPD/SIRPα ligation activates the Mitogen-Activated Protein Kinase (MAPK)/Extracellular Signal-Related Kinase (ERK) signal cascade; ERK downregulates Interferon Regulatory Factor 1 (IRF1) expression. Consequently, the SPD/SIRPα signaling pathway decreases IL-12p40 production in human macrophages after exposure to LPS. IL-12p40 is a key immunoregulatory factor in bacterial infection that promotes production of IFNγ by T lymphocytes. Pulmonary fibroblasts are activated by IL-4/IL-4R ligation. IFNγ induces IRF1 via STAT1 signaling, and IRF1 acts as the promoter repressor of IL-4 to attenuate its production. IFNγ also inhibits IL-4R expression. A reduction in IFNγ induced by IL-12p40 deficiency via the SPD/SIRPα signaling pathway enhances IL-4 and IL-4R expression to augment the activity of fibroblasts. This finding indicates that pulmonary fibrosis is exacerbated by SPD/SIRPα signaling during bacterial infection.","PeriodicalId":91526,"journal":{"name":"Journal of AIDS and immune research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2021-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74865040","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}

引用次数: 0

Effect of Fingolimod on the Frequency of Regulatory T Cells in Patients with Relapsing-Remitting Multiple Sclerosis 芬戈莫德对复发-缓解型多发性硬化患者调节性T细胞频率的影响

Journal of AIDS and immune research Pub Date : 2018-08-10 DOI: 10.26420/jimmunres.2018.1032

A. F.

引用次数: 3

Newborn Hearing Screenings in Human Immunodeficiency Virus-Exposed Uninfected Infants. 人类免疫缺陷病毒暴露的未感染婴儿的新生儿听力筛查

Journal of AIDS and immune research Pub Date : 2016-01-01 Epub Date: 2016-09-05

P Torre, B Zeldow, T J Yao, H J Hoffman, G K Siberry, M U Purswani, T Frederick, S A Spector, P L Williams

{"title":"Newborn Hearing Screenings in Human Immunodeficiency Virus-Exposed Uninfected Infants.","authors":"P Torre, B Zeldow, T J Yao, H J Hoffman, G K Siberry, M U Purswani, T Frederick, S A Spector, P L Williams","doi":"","DOIUrl":"","url":null,"abstract":"Perinatal HIV infection and congenital cytomegalovirus (CMV) infection may increase the risk for hearing loss. We examined 1,435 infants enrolled in the Surveillance Monitoring of ART Toxicities (SMARTT) study of the Pediatric HIV/AIDS Cohort Study (PHACS) network, a prospective study of the safety of in utero antiretroviral (ARV) exposures. We determined the proportion of perinatally HIV-exposed uninfected (HEU) newborns who were referred for additional hearing testing, and evaluated the association between in utero ARV exposures and newborn hearing screening results. Using a nested case-control design, we also examined congenital CMV infection in infants with and without screening referral. Congenital CMV infection was determined based on CMV DNA detection using a nested PCR assay in peripheral blood mononuclear cells obtained within 14 days of birth. Among the 1,435 infants (70% black, 31% Hispanic, 51% male), 45 (3.1%) did not pass the hearing screen and were referred for further hearing testing. Based on exact logistic regression models controlling for maternal use of tobacco and ototoxic medications, first trimester exposure to Tenofovir was associated with lower odds of a newborn hearing screening referral [adjusted odds ratio (aOR) = 0.41, 95% confidence interval (CI): 0.14-1.00]. Exposure to Atazanavir was linked to higher odds of newborn screening referral, although not attaining significance [aOR = 1.84, 95% CI: 0.92-3.56]. Maternal ARV use may have varying effects on newborn hearing screenings. These results highlight the importance for audiologists to be knowledgeable of in utero ARV exposures in HEU children because of the possibility of higher referrals in these children.","PeriodicalId":91526,"journal":{"name":"Journal of AIDS and immune research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34957856","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

Forced Complementation between Subgenomic RNAs: Does Human Immunodeficiency Type 1 Virus Reverse Transcription Occur in Viral Core, Cytoplasm, or Early Endosome? 亚基因组rna之间的强制互补:人类免疫缺陷1型病毒逆转录是否发生在病毒核心、细胞质或早期内体?

Journal of AIDS and immune research Pub Date : 2015-01-01 Epub Date: 2015-03-02

Weining Han, Yuejin Li, Bernard S Bagaya, Meijuan Tian, Mastooreh Chamanian, Chuanwu Zhu, Jie Shen, Yong Gao

{"title":"Forced Complementation between Subgenomic RNAs: Does Human Immunodeficiency Type 1 Virus Reverse Transcription Occur in Viral Core, Cytoplasm, or Early Endosome?","authors":"Weining Han, Yuejin Li, Bernard S Bagaya, Meijuan Tian, Mastooreh Chamanian, Chuanwu Zhu, Jie Shen, Yong Gao","doi":"","DOIUrl":"","url":null,"abstract":"Although the process of reverse transcription is well elucidated, it remains unclear if viral core disruption provides a more cellular or viral milieu for HIV-1 reverse transcription. We have devised a method to require mixing of viral cores or core constituents to produce infectious progeny virus by a bipartite subgenomic RNA (sgRNA) system, in which HIV-1 cplt_R/U5/gag/Δpol and nfl sgRNAs are complementary to each other and when together can complete viral reverse transcription. Only the heterodiploid virus containing both the nfl and cplt_R/U5/gag/Δpol sgRNAs can complete reverse transcription and propagate infectious virus upon de novo infection. Dual exposure of U87.CD4.CXCR4 cells with high titers of the homodimeric nfl and cplt_R/U5/gag/Δpol virus particles did not result in productive virus infection. On the other hand, in early endosomes, the HIV-1 sgRNAs released from viral cores can retain function and complete the reverse transcription and result in productive infection. These findings confirm the assumptions that, in natural infection, HIV-1 cores, and likely other retrovirus cores, remain largely intact and do not mix/fuse in the cytoplasm during the reverse transcription process, and circulating cytoplasmic HIV-1 sgRNA (produced through transfection) could not help the complementary sgRNA in the viral core to complement the reverse transcription process.","PeriodicalId":91526,"journal":{"name":"Journal of AIDS and immune research","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882926/pdf/nihms723306.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34435640","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