In this paper,we study a mathematical model of Hepatitis C Virus(HCV)infection.We present a compartmental mathematical model involving healthy hepatocytes,infected hepatocytes,non-activated dendritic cells,activated d...In this paper,we study a mathematical model of Hepatitis C Virus(HCV)infection.We present a compartmental mathematical model involving healthy hepatocytes,infected hepatocytes,non-activated dendritic cells,activated dendritic cells and cytotoxic T lymphocytes.The derivative used is of non-local fractional order and with non-singular kernel.The existence and uniqueness of the system is proven and its stability is analyzed.Then,by applying the Laplace Adomian decomposition method for the fractional derivative,we present the semi-analytical solution of the model.Finally,some numerical simulations are performed for concrete values of the parameters and several graphs are plotted to reveal the qualitative properties of the solutions.展开更多
Arthropod-borne chikungunya virus(CHIKV)infection can cause a debilitating arthritic disease in human.However,there are no specific antiviral drugs and effective licensed vaccines against CHIKV available for clinical ...Arthropod-borne chikungunya virus(CHIKV)infection can cause a debilitating arthritic disease in human.However,there are no specific antiviral drugs and effective licensed vaccines against CHIKV available for clinical use.Here,we developed an m RNA-lipid nanoparticle(m RNA-LNP)vaccine expressing CHIKV E2-E1 antigen,and compared its immunogenicity with soluble recombinant protein s E2-E1 antigen expressed in S2 cells.For comparison,we first showed that recombinant protein antigens mixed with aluminum adjuvant elicit strong antigenspecific humoral immune response and a moderate cellular immune response in C57BL/6 mice.Moreover,s E2-E1vaccine stimulated 12-23 folds more neutralizing antibodies than s E1 vaccine and s E2 vaccine.Significantly,when E2-E1 gene was delivered by an m RNA-LNP vaccine,not only the better magnitude of neutralizing antibody responses was induced,but also greater cellular immune responses were generated,especially for CD8+T cell responses.Moreover,E2-E1-LNP induced CD8~+T cells can perform cytotoxic effect in vivo.Considering its better immunogenicity and convenience of preparation,we suggest that more attention should be placed to develop CHIKV E2-E1-LNP m RNA vaccine.展开更多
目的筛选和鉴定人乳头状瘤病毒11型E7抗原（HPV11E7）HLA-A＊0201限制性细胞毒性T淋巴细胞（cytotoxic T lymphocyte，CTL）表位。方法预测HPV11E7抗原HLA-A＊0201限制性CTL表位并合成相对应的表位多肽和四聚体（tetramer），即HPV11E7 ...目的筛选和鉴定人乳头状瘤病毒11型E7抗原（HPV11E7）HLA-A＊0201限制性细胞毒性T淋巴细胞（cytotoxic T lymphocyte，CTL）表位。方法预测HPV11E7抗原HLA-A＊0201限制性CTL表位并合成相对应的表位多肽和四聚体（tetramer），即HPV11E7 7-15（TLKDIVLDL）、15-23（LQPPDPVGL）、47-55（PLTQHYQIL）、81-89（DLLLGTLNI）和82-90（LLLGTLNIV）。从健康HLA-A＊0201成人外周血单一核细胞诱导树突状细胞（DC）并负载上述表位多肽，流式细胞技术检测DC成熟分化标记及ELISA法检测DC分泌的IL-12；成熟DC负载各组多肽后观察DC激活T淋巴细胞的效应，ELISA法检测T细胞分泌的IFN-γ；四聚体检测抗原特异性CD8^＋T细胞及乳酸脱氢酶（LDH）释放法评价DC诱导的CTL对靶细胞的特异性体外杀伤效应。结果预测的5条HPV11ET表位多肽均能诱导DC的成熟分化；E77-15、82-90和15-23多肽负载的DC能激活T淋巴细胞分泌高水平IFN-γ；E77-15多肽负载的DC能刺激特异性tetramer^＋CD8^＋细胞增殖且其诱导的CTL对HPV11E7／293细胞产生高效率的特异性杀伤作用（P〈0．05）。结论筛选并鉴定出1条HPV11E7HL-A＊0201限制性CTL表位E77-15（TLKDIVLDL），负载该表位肽的DC体外可诱导高效、特异性的CTL效应，抗原性较强，有可能作为HPV感染治疗用肽疫苗的候选表位。展开更多
Human immunodeficiency virus(HIV)has had an insightful impact about the state of healthiness of human immune system.Due to great improvement in drug therapy,HIV infections have been reduced by 17%over the past eight y...Human immunodeficiency virus(HIV)has had an insightful impact about the state of healthiness of human immune system.Due to great improvement in drug therapy,HIV infections have been reduced by 17%over the past eight years.It has been proved that most effective treatment HAART(Highly Active Anti Retroviral Therapy)mainly controls the diseases progression but it does not eradicate the diseases completely.Reverse Transcriptase Inhibitor drugs specially associated with virus specific Cytotoxic T-Lymphocyte(CTL)that declines with disease progression. CTL responses against AIDS pathogenesis could be potential in the dynamics of virus replication, recognition and clearance of infected cells.In this research article a mathematical model has been proposed on the basis of CTL response suppression in the chronic phase of infection due to presence of virus.We also consider the growth of the virus population from the infected CD4^+T cells budding process and from the other infected cells like macrophages and thymocytes.Our analytical and numerical studies are consistent with existing observations from allied areas.展开更多
基金supported by the Agencia Estatal de Investigacin(AEI)of Spain,co-financed by the European Fund for Regional Development(FEDER)corresponding to the 2014-2020 multiyear financial framework,project PID2020-113275GB-I00Instituto de Salud Carlos II,grant COV20/00617Xunta de Galicia under grant ED431C 2019/02.
文摘In this paper,we study a mathematical model of Hepatitis C Virus(HCV)infection.We present a compartmental mathematical model involving healthy hepatocytes,infected hepatocytes,non-activated dendritic cells,activated dendritic cells and cytotoxic T lymphocytes.The derivative used is of non-local fractional order and with non-singular kernel.The existence and uniqueness of the system is proven and its stability is analyzed.Then,by applying the Laplace Adomian decomposition method for the fractional derivative,we present the semi-analytical solution of the model.Finally,some numerical simulations are performed for concrete values of the parameters and several graphs are plotted to reveal the qualitative properties of the solutions.
基金supported by the following grants:the National Key R&D Program of China(Grant 2016YFC1201000 to X.J.)the Institute Fund of Shanghai Public Health Clinical Center(Grant KY-GW-2021-17 to ZH.L.)。
文摘Arthropod-borne chikungunya virus(CHIKV)infection can cause a debilitating arthritic disease in human.However,there are no specific antiviral drugs and effective licensed vaccines against CHIKV available for clinical use.Here,we developed an m RNA-lipid nanoparticle(m RNA-LNP)vaccine expressing CHIKV E2-E1 antigen,and compared its immunogenicity with soluble recombinant protein s E2-E1 antigen expressed in S2 cells.For comparison,we first showed that recombinant protein antigens mixed with aluminum adjuvant elicit strong antigenspecific humoral immune response and a moderate cellular immune response in C57BL/6 mice.Moreover,s E2-E1vaccine stimulated 12-23 folds more neutralizing antibodies than s E1 vaccine and s E2 vaccine.Significantly,when E2-E1 gene was delivered by an m RNA-LNP vaccine,not only the better magnitude of neutralizing antibody responses was induced,but also greater cellular immune responses were generated,especially for CD8+T cell responses.Moreover,E2-E1-LNP induced CD8~+T cells can perform cytotoxic effect in vivo.Considering its better immunogenicity and convenience of preparation,we suggest that more attention should be placed to develop CHIKV E2-E1-LNP m RNA vaccine.
文摘目的筛选和鉴定人乳头状瘤病毒11型E7抗原（HPV11E7）HLA-A＊0201限制性细胞毒性T淋巴细胞（cytotoxic T lymphocyte，CTL）表位。方法预测HPV11E7抗原HLA-A＊0201限制性CTL表位并合成相对应的表位多肽和四聚体（tetramer），即HPV11E7 7-15（TLKDIVLDL）、15-23（LQPPDPVGL）、47-55（PLTQHYQIL）、81-89（DLLLGTLNI）和82-90（LLLGTLNIV）。从健康HLA-A＊0201成人外周血单一核细胞诱导树突状细胞（DC）并负载上述表位多肽，流式细胞技术检测DC成熟分化标记及ELISA法检测DC分泌的IL-12；成熟DC负载各组多肽后观察DC激活T淋巴细胞的效应，ELISA法检测T细胞分泌的IFN-γ；四聚体检测抗原特异性CD8^＋T细胞及乳酸脱氢酶（LDH）释放法评价DC诱导的CTL对靶细胞的特异性体外杀伤效应。结果预测的5条HPV11ET表位多肽均能诱导DC的成熟分化；E77-15、82-90和15-23多肽负载的DC能激活T淋巴细胞分泌高水平IFN-γ；E77-15多肽负载的DC能刺激特异性tetramer^＋CD8^＋细胞增殖且其诱导的CTL对HPV11E7／293细胞产生高效率的特异性杀伤作用（P〈0．05）。结论筛选并鉴定出1条HPV11E7HL-A＊0201限制性CTL表位E77-15（TLKDIVLDL），负载该表位肽的DC体外可诱导高效、特异性的CTL效应，抗原性较强，有可能作为HPV感染治疗用肽疫苗的候选表位。
基金Research is supported by the Government of India,Ministry of Science and Technology,Mathematical Science office,No.SR/S4/MS:558/08
文摘Human immunodeficiency virus(HIV)has had an insightful impact about the state of healthiness of human immune system.Due to great improvement in drug therapy,HIV infections have been reduced by 17%over the past eight years.It has been proved that most effective treatment HAART(Highly Active Anti Retroviral Therapy)mainly controls the diseases progression but it does not eradicate the diseases completely.Reverse Transcriptase Inhibitor drugs specially associated with virus specific Cytotoxic T-Lymphocyte(CTL)that declines with disease progression. CTL responses against AIDS pathogenesis could be potential in the dynamics of virus replication, recognition and clearance of infected cells.In this research article a mathematical model has been proposed on the basis of CTL response suppression in the chronic phase of infection due to presence of virus.We also consider the growth of the virus population from the infected CD4^+T cells budding process and from the other infected cells like macrophages and thymocytes.Our analytical and numerical studies are consistent with existing observations from allied areas.
