Current treatments for chronic hepatitis B(CHB)are lifelong,often accompanied by side effects and the risk of drug resistance,highlighting the urgent need for alternative therapies such as therapeutic vaccines.However...Current treatments for chronic hepatitis B(CHB)are lifelong,often accompanied by side effects and the risk of drug resistance,highlighting the urgent need for alternative therapies such as therapeutic vaccines.However,challenges such as selecting appropriate antigens and addressing multiple hepatitis B virus(HBV)genotypes hinder the development of these vaccines.One approach to overcoming these challenges is reverse vaccinology(RV)combined with immunoinformatics.RV uses computational methods to identify antigens from pathogen genetic information,including genomic and proteomic data.These methods have helped researchers identify conserved epitopes across bacterial strains or viral species,including multiple HBV genotypes.Computational tools,such as epitope mapping algorithms,molecular docking analysis,molecular dynamics simulations,and immune response simulations,enable key epitope identification,predict vaccine candidates'binding potential to immune cell receptors,and forecast the immune response.Together,these approaches streamline therapeutic vaccine design for CHB,making it faster,more cost-effective,and accurate.This review aims to explore the potential role of RV and immunoinformatics in advancing therapeutic vaccine design for CHB.展开更多
Clostridioides difficile(C.difficile),as the major pathogen of diarrhea in healthcare settings,has become increasingly prevalent within community populations,resulting in significant morbidity and mortality.However,th...Clostridioides difficile(C.difficile),as the major pathogen of diarrhea in healthcare settings,has become increasingly prevalent within community populations,resulting in significant morbidity and mortality.However,the therapeutic options for Clostridioides difficile infection(CDI)remain limited,and as of now,no authorized vaccine is available to combat this disease.Therefore,the development of a novel vaccine against C.difficile is of paramount importance.In our study,the complete proteome sequences of 118 strains of C.difficile were downloaded and analyzed.We found four antigenic proteins that were highly conserved and can be used for epitope identification.We designed two vaccines,WLcd1 and WLcd2,that contain the ideal T-cell and B-cell epitopes,adjuvants,and the pan HLA DR-binding epitope(PADRE)sequences.The biophysical and chemical assessments of these vaccine candidates indicated that they were suitable for immunogenic applications.Molecular docking analyses revealed that WLcd1 bonded with higher affinity to Toll-like receptors(TLRs)than WLcd2.Furthermore,molecular dynamics(MD)simulations,performed using Gmx_MMPBSA v1.56,confirmed the binding stability of WLcd1 with TLR2 and TLR4.The preliminary findings suggested that this multi-epitope vaccine could be a promising candidate for protection against CDI;however,experimental studies are necessary to confirm these predictions.展开更多
Objectives:Cronobacter sakazakii,formerly Enterobacter sakazakii,is an emerging ubiquitous and opportunistic foodborne pathogen with a high mortality rate.It has been implicated in cases of meningitis,septicaemia,and ...Objectives:Cronobacter sakazakii,formerly Enterobacter sakazakii,is an emerging ubiquitous and opportunistic foodborne pathogen with a high mortality rate.It has been implicated in cases of meningitis,septicaemia,and necrotizing enterocolitis among infants worldwide in association with powdered infant formula(PIF).This study was an insilico designed peptide base kit framework,using immunoinformatic techniques for quick detection of C.sakazakii in PIF.Materials and Methods:In the present study,a peptide-based kit was designed with a bioinformatic technique to rapidly identify C.sakazakii in PIF using fhE,secY,and bcsC,which are genes responsible for its bioflm formation,as target genes.The antigenicity,membrane topology,and the presence of signal peptides of the target genes were analysed using VaxiJen,DeepTMHMM,and SignalP servers.To provide stability and fexibility to the multiple-epitope construct,the linear B cells and helper T cells(IL-4(interleukin 4)and IL-10(interleukin 10)inducing epitopes)were linked with a GSGSG linker followed by the addition of protein disulphide bonds.To ascertain specifcity,the multi-epitope construct was molecularly docked against genes from sources other than PIF,like alfalfa,and the environment,with PIF being the highest:–328.48.Finally,the codons were modifed using the pET28a(+)vector,and the resultant multi-epitope construct was successfully cloned in silico.Results:The fnal construct had a length of 486 bp,an instability index of 23.26,a theoretical pI of 9.34,a molecular weight of 16.5 kDa,and a Z-score of–3.41.Conclusions:The multi-epitope peptide construct could be a conceptual framework for creating a C.sakazakii peptide-based detection kit,which has the potential to provide fast and effcient detection.However,there is a need for additional validation through the in vitro and in vivo techniques.展开更多
Respiratory syncytial virus(RSV)poses a significant global health threat,especially affecting infants and the elderly.Addressing this,the present study proposes an innovative approach to vaccine design,utilizing immun...Respiratory syncytial virus(RSV)poses a significant global health threat,especially affecting infants and the elderly.Addressing this,the present study proposes an innovative approach to vaccine design,utilizing immunoinformatics and computational strategies.We analyzed RSV's structural proteins across both subtypes A and B,identifying potential helper T lymphocyte,cytotoxic T lymphocyte,and linear B lymphocyte epitopes.Criteria such as antigenicity,allergenicity,toxicity,and cytokine-inducing potential were rigorously examined.Additionally,we evaluated the conservancy of these epitopes and their population coverage across various RSV strains.The comprehensive analysis identified six major histocompatibility complex class I(MHC-I)binding,five MHC-II binding,and three B-cell epitopes.These were integrated with suitable linkers and adjuvants to form the vaccine.Further,molecular docking and molecular dynamics simulations demonstrated stable interactions between the vaccine candidate and human Toll-like receptors(TLR4 and TLR5),with a notable preference for TLR4.Immune simulation analysis underscored the vaccine's potential to elicit a strong immune response.This study presents a promising RSV vaccine candidate and offers theoretical support,marking a significant advancement in vaccine development efforts.However,the promising in silico findings need to be further validated through additional in vivo studies.展开更多
Objective To introduce the recent developments in cancer immunoinformatics with an emphasis on the latest trends and future direction.Data sources All related articles in this review were searched from PubMed publishe...Objective To introduce the recent developments in cancer immunoinformatics with an emphasis on the latest trends and future direction.Data sources All related articles in this review were searched from PubMed published in English from 1992 to 2013. The search terms were cancer, immunoinformatics, immunological databases, and computational vaccinology.Study selection Original articles and reviews those were related to application of cancer immunoinformatics about tumor basic and clinical research were selected.Results Cancer immunoinformatics has been widely researched and applied in a series of fields of cancer research, including computational tools for cancer, cancer immunological databases, computational vaccinology, and cancer diagnostic workflows. Furthermore, the improvement of its theory and technology brings an enlightening insight into understanding and researching cancer and helps expound more deep and complete mechanisms of tumorigenesis and progression.Conclusion Cancer immunoinformatics provides promising methods and novel strategies for the discovery and development of tumor basic and clinical research.展开更多
Recombinant technology-based vaccines have emerged as a highly effective way to prevent a wide range of illnesses.The technology improved vaccine manufacturing,rendering it more efficient and economical.These vaccines...Recombinant technology-based vaccines have emerged as a highly effective way to prevent a wide range of illnesses.The technology improved vaccine manufacturing,rendering it more efficient and economical.These vaccines have multiple advantages compared to conventional vaccines.The pandemic has heightened awareness of the advantages of these vaccine technologies;trust and acceptance of these vaccines are steadily growing globally.This work offers an overview of the prospects and advantages associated with recombinant vaccines.Additionally,it discusses some of the challenges likely to arise in the future.Their ability to target diverse pathogen classes underscores their contributions to preventing previously untreatable diseases(especially vector-borne and emerging diseases)and hurdles faced throughout the vaccine development process,especially in enhancing the effectiveness of these vaccines.Moreover,their compatibility with emerging vaccination platforms of the future like virus-like particles and CRISPR/Cas9 for the production of next-generation vaccines may offer many prospects.This review also reviewed the hurdles faced throughout the vaccine development process,especially in enhancing the effectiveness of these vaccines against vector-borne diseases,emerging diseases,and untreatable diseases with high mortality rates like AIDS as well as cancer.展开更多
Bovine coronavirus(BCoV)poses a significant threat to the global cattle industry,causing both respiratory and gastrointestinal infections in cattle populations.This necessitates the development of efficacious vaccines...Bovine coronavirus(BCoV)poses a significant threat to the global cattle industry,causing both respiratory and gastrointestinal infections in cattle populations.This necessitates the development of efficacious vaccines.While several inactivated and live BCoV vaccines exist,they are predominantly limited to calves.The immunization of adult cattle is imperative for BCoV infection control,as it curtails viral transmission to calves and ameliorates the impact of enteric and respiratory ailments across all age groups within the herd.This study presents an in silico methodology for devising a multiepitope vaccine targeting BCoV.The spike glycoprotein(S)and nucleocapsid(N)proteins,which are integral elements of the BCoV structure,play pivotal roles in the viral infection cycle and immune response.We constructed a remarkably effective multiepitope vaccine candidate specifically designed to combat the BCoV population.Using immunoinformatics technology,B-cell and T-cell epitopes were predicted and linked together using linkers and adjuvants to efficiently trigger both cellular and humoral immune responses in cattle.The in silico construct was characterized,and assessment of its physicochemical properties revealed the formation of a stable vaccine construct.After 3D modeling of the vaccine construct,molecular docking revealed a stable interaction with the bovine receptor bTLR4.Moreover,the viability of the vaccine’s high expression and simple purification was demonstrated by codon optimization and in silico cloning expression into the pET28a(+)vector.By applying immunoinformatics approaches,researchers aim to better understand the immune response to bovine coronavirus,discover potential targets for intervention,and facilitate the development of diagnostic tools and vaccines to mitigate the impact of this virus on cattle health and the livestock industry.We anticipate that the design will be useful as a preventive treatment for BCoV sickness in cattle,opening the door for further laboratory studies.展开更多
Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus ha...Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus have shown the peculiar capability to modulate both innate and adaptive immune responses. In particular, HLA class Ⅰmolecules are recognized by CD8+ T-cells and natural killers(NK) cells towards the interaction with T cell receptor(TCR) and Killer Immunoglobulin Receptor(KIR) 3DL1 respectively. Polymorphisms within the different HLA alleles generate structural changes in HLA classⅠpeptide-binding pockets. Amino acid changes in the peptide-binding pocket lead to the presentation of a different set of peptides to T and NK cells. This review summarizes the role of HLA in HIV progression toward acquired immunodeficiency disease syndrome and its receptors. Recently, many studies have been focused on determining the HLA binding-peptides. The novel use of immune-informatics tools, from the prediction of the HLA-bound peptides to the modification of the HLAreceptor complexes, is considered. A better knowledge of HLA peptide presentation and recognition are allowing new strategies for immune response manipulation to be applied against HIV virus.展开更多
Background:Diagnosing latent tuberculosis(TB)infection(LTBI)and active TB(ATB)is crucial for preventing disease progression and transmission.However,current diagnostic tests have limitations in terms of accuracy and s...Background:Diagnosing latent tuberculosis(TB)infection(LTBI)and active TB(ATB)is crucial for preventing disease progression and transmission.However,current diagnostic tests have limitations in terms of accuracy and sensitivity,making it challenging to diagnose these different infection states.Therefore,this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic tests.Methods:We developed a novelmultiepitope-based diagnostic biomarker(MEBDB)fromLTBI region of differentiation antigens using bioinformatics and immunoinformatics.Immune responses induced byMEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead assays.This study was conducted from April 2022 to December 2022 in the SeniorDepartment of Tuberculosis at the 8thMedical Center of PLA General Hospital,China.Blood samples were collected from participants with ATB,individuals with LTBI,and healthy controls(HCs).The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic curves.Results:A novel MEBDB,designated as CP19128P,was generated.CP19128P comprises 19 helper T lymphocyte epitopes,12 cytotoxic T lymphocyte epitopes,and 8 B-cell epitopes.In silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune responses.CP19128P generated significantly higher levels of tumor necrosis factor(TNF-α),interleukin 4(IL-4),and IL-10 in ATB patients(n=7)and LTBI(n=8)individuals compared with HCs(n=62)(P<0.001).Moreover,CP19128P-induced specific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and specificity.Combining IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs(the area under the receiver operating characteristic curve[AUC],0.976[95% confidence interval[CI],0.934-1.000]or 0.986[0.956-1.000]),whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from HCs(AUC,0.887[0.782-0.993]or 0.984[0.958-1.000]).Conclusions:Our study revealed that CP19128P is a potential MEBDBfor the diagnosis of LTBI andATB.Our findings suggest a promising strategy for developing novel,accurate,and sensitive diagnostic biomarkers and identifying new targets for TB diagnosis and management.展开更多
Background:Coronavirus disease 2019(COVID-19)linked with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)cause severe illness and life-threatening pneumonia in humans.The current COVID-19 pandemic demands a...Background:Coronavirus disease 2019(COVID-19)linked with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)cause severe illness and life-threatening pneumonia in humans.The current COVID-19 pandemic demands an effective vaccine to acquire protection against the infection.Therefore,the present study was aimed to design a multiepitope-based subunit vaccine(MESV)against COVID-19.Methods:Structural proteins(Surface glycoprotein,Envelope protein,and Membrane glycoprotein)of SARS-CoV-2 are responsible for its prime functions.Sequences of proteins were downloaded from GenBank and several immunoinformatics coupled with computational approaches were employed to forecast B-and T-cell epitopes from the SARS-CoV-2 highly antigenic structural proteins to design an effective MESV.Results:Predicted epitopes suggested high antigenicity,conserveness,substantial interactions with the human leukocyte antigen(HLA)binding alleles,and collective global population coverage of 88.40%.Taken together,276 amino acids long MESV was designed by connecting 3 cytotoxic T lymphocytes(CTL),6 helper T lymphocyte(HTL)and 4 B-cell epitopes with suitable adjuvant and linkers.The MESV construct was non-allergenic,stable,and highly antigenic.Molecular docking showed a stable and high binding affinity of MESV with human pathogenic toll-like receptors-3(TLR3).Furthermore,in silico immune simulation revealed significant immunogenic response of MESV.Finally,MEV codons were optimized for its in silico cloning into the Escherichia coli K-12 system,to ensure its increased expression.Conclusion:The MESV developed in this study is capable of generating immune response against COVID-19.Therefore,if designed MESV further investigated experimentally,it would be an effective vaccine candidate against SARS-CoV-2 to control and prevent COVID-19.展开更多
Cancer immunotherapy has now been conclusively shown to be capable of producing durable responses for a substantial number of patients.Adoptive cell transfer and checkpoint blockade therapies in particular both demons...Cancer immunotherapy has now been conclusively shown to be capable of producing durable responses for a substantial number of patients.Adoptive cell transfer and checkpoint blockade therapies in particular both demonstrate that antigen-specific immune responses can be dramatically effective,even in previously refractory late stage disease.Such developments,together with advances in technology,have strongly encouraged revisiting the concept of neoantigen vaccines.Here we introduce basic ideas in the field to allow investigators from diverse backgrounds to understand these developments,grasp current issues,and contribute to further progress.展开更多
基金Supported by Riset Unggulan of Institut Teknologi Bandung,No.125/IT1.B07.1/SPP-DRI/Ⅲ/2025.
文摘Current treatments for chronic hepatitis B(CHB)are lifelong,often accompanied by side effects and the risk of drug resistance,highlighting the urgent need for alternative therapies such as therapeutic vaccines.However,challenges such as selecting appropriate antigens and addressing multiple hepatitis B virus(HBV)genotypes hinder the development of these vaccines.One approach to overcoming these challenges is reverse vaccinology(RV)combined with immunoinformatics.RV uses computational methods to identify antigens from pathogen genetic information,including genomic and proteomic data.These methods have helped researchers identify conserved epitopes across bacterial strains or viral species,including multiple HBV genotypes.Computational tools,such as epitope mapping algorithms,molecular docking analysis,molecular dynamics simulations,and immune response simulations,enable key epitope identification,predict vaccine candidates'binding potential to immune cell receptors,and forecast the immune response.Together,these approaches streamline therapeutic vaccine design for CHB,making it faster,more cost-effective,and accurate.This review aims to explore the potential role of RV and immunoinformatics in advancing therapeutic vaccine design for CHB.
基金upported by the National Key Research and Development Program of China[No.2022YFC2009801,No.2022YFC2009805]the Natural Science Foundation of Hunan Province[No.2021JJ31071]+2 种基金the Project program of National Clinical Research Center for Geriatric Disorders(Xiangya Hospital)[No.2021KFJJ05]Health Development Research Center of the National Health Commission,"Evidence-based Evaluation and Demonstration Base Construction Project of Infection Control Measures in Healthcare Institutions"[No.CNHDRC-KJ-L-2020-53-04375]Scientific and technological personnel lifting Project in Hunan Province[No.2023 TJ-Z11].
文摘Clostridioides difficile(C.difficile),as the major pathogen of diarrhea in healthcare settings,has become increasingly prevalent within community populations,resulting in significant morbidity and mortality.However,the therapeutic options for Clostridioides difficile infection(CDI)remain limited,and as of now,no authorized vaccine is available to combat this disease.Therefore,the development of a novel vaccine against C.difficile is of paramount importance.In our study,the complete proteome sequences of 118 strains of C.difficile were downloaded and analyzed.We found four antigenic proteins that were highly conserved and can be used for epitope identification.We designed two vaccines,WLcd1 and WLcd2,that contain the ideal T-cell and B-cell epitopes,adjuvants,and the pan HLA DR-binding epitope(PADRE)sequences.The biophysical and chemical assessments of these vaccine candidates indicated that they were suitable for immunogenic applications.Molecular docking analyses revealed that WLcd1 bonded with higher affinity to Toll-like receptors(TLRs)than WLcd2.Furthermore,molecular dynamics(MD)simulations,performed using Gmx_MMPBSA v1.56,confirmed the binding stability of WLcd1 with TLR2 and TLR4.The preliminary findings suggested that this multi-epitope vaccine could be a promising candidate for protection against CDI;however,experimental studies are necessary to confirm these predictions.
文摘Objectives:Cronobacter sakazakii,formerly Enterobacter sakazakii,is an emerging ubiquitous and opportunistic foodborne pathogen with a high mortality rate.It has been implicated in cases of meningitis,septicaemia,and necrotizing enterocolitis among infants worldwide in association with powdered infant formula(PIF).This study was an insilico designed peptide base kit framework,using immunoinformatic techniques for quick detection of C.sakazakii in PIF.Materials and Methods:In the present study,a peptide-based kit was designed with a bioinformatic technique to rapidly identify C.sakazakii in PIF using fhE,secY,and bcsC,which are genes responsible for its bioflm formation,as target genes.The antigenicity,membrane topology,and the presence of signal peptides of the target genes were analysed using VaxiJen,DeepTMHMM,and SignalP servers.To provide stability and fexibility to the multiple-epitope construct,the linear B cells and helper T cells(IL-4(interleukin 4)and IL-10(interleukin 10)inducing epitopes)were linked with a GSGSG linker followed by the addition of protein disulphide bonds.To ascertain specifcity,the multi-epitope construct was molecularly docked against genes from sources other than PIF,like alfalfa,and the environment,with PIF being the highest:–328.48.Finally,the codons were modifed using the pET28a(+)vector,and the resultant multi-epitope construct was successfully cloned in silico.Results:The fnal construct had a length of 486 bp,an instability index of 23.26,a theoretical pI of 9.34,a molecular weight of 16.5 kDa,and a Z-score of–3.41.Conclusions:The multi-epitope peptide construct could be a conceptual framework for creating a C.sakazakii peptide-based detection kit,which has the potential to provide fast and effcient detection.However,there is a need for additional validation through the in vitro and in vivo techniques.
基金The authors are thankful to the Research Institute of Agriculture and Life Sciences,Seoul National University,and the BK21 FOUR Program of the Department of Agricultural Biotechnology,Seoul National University,Seoul,Republic of Korea,for supporting the research workThis research was supported by a fund(Project Code No.Z-1543082-2019-20-01)by Research of Animal and Plant Quarantine Agency,Republic of Korea.
文摘Respiratory syncytial virus(RSV)poses a significant global health threat,especially affecting infants and the elderly.Addressing this,the present study proposes an innovative approach to vaccine design,utilizing immunoinformatics and computational strategies.We analyzed RSV's structural proteins across both subtypes A and B,identifying potential helper T lymphocyte,cytotoxic T lymphocyte,and linear B lymphocyte epitopes.Criteria such as antigenicity,allergenicity,toxicity,and cytokine-inducing potential were rigorously examined.Additionally,we evaluated the conservancy of these epitopes and their population coverage across various RSV strains.The comprehensive analysis identified six major histocompatibility complex class I(MHC-I)binding,five MHC-II binding,and three B-cell epitopes.These were integrated with suitable linkers and adjuvants to form the vaccine.Further,molecular docking and molecular dynamics simulations demonstrated stable interactions between the vaccine candidate and human Toll-like receptors(TLR4 and TLR5),with a notable preference for TLR4.Immune simulation analysis underscored the vaccine's potential to elicit a strong immune response.This study presents a promising RSV vaccine candidate and offers theoretical support,marking a significant advancement in vaccine development efforts.However,the promising in silico findings need to be further validated through additional in vivo studies.
文摘Objective To introduce the recent developments in cancer immunoinformatics with an emphasis on the latest trends and future direction.Data sources All related articles in this review were searched from PubMed published in English from 1992 to 2013. The search terms were cancer, immunoinformatics, immunological databases, and computational vaccinology.Study selection Original articles and reviews those were related to application of cancer immunoinformatics about tumor basic and clinical research were selected.Results Cancer immunoinformatics has been widely researched and applied in a series of fields of cancer research, including computational tools for cancer, cancer immunological databases, computational vaccinology, and cancer diagnostic workflows. Furthermore, the improvement of its theory and technology brings an enlightening insight into understanding and researching cancer and helps expound more deep and complete mechanisms of tumorigenesis and progression.Conclusion Cancer immunoinformatics provides promising methods and novel strategies for the discovery and development of tumor basic and clinical research.
文摘Recombinant technology-based vaccines have emerged as a highly effective way to prevent a wide range of illnesses.The technology improved vaccine manufacturing,rendering it more efficient and economical.These vaccines have multiple advantages compared to conventional vaccines.The pandemic has heightened awareness of the advantages of these vaccine technologies;trust and acceptance of these vaccines are steadily growing globally.This work offers an overview of the prospects and advantages associated with recombinant vaccines.Additionally,it discusses some of the challenges likely to arise in the future.Their ability to target diverse pathogen classes underscores their contributions to preventing previously untreatable diseases(especially vector-borne and emerging diseases)and hurdles faced throughout the vaccine development process,especially in enhancing the effectiveness of these vaccines.Moreover,their compatibility with emerging vaccination platforms of the future like virus-like particles and CRISPR/Cas9 for the production of next-generation vaccines may offer many prospects.This review also reviewed the hurdles faced throughout the vaccine development process,especially in enhancing the effectiveness of these vaccines against vector-borne diseases,emerging diseases,and untreatable diseases with high mortality rates like AIDS as well as cancer.
文摘Bovine coronavirus(BCoV)poses a significant threat to the global cattle industry,causing both respiratory and gastrointestinal infections in cattle populations.This necessitates the development of efficacious vaccines.While several inactivated and live BCoV vaccines exist,they are predominantly limited to calves.The immunization of adult cattle is imperative for BCoV infection control,as it curtails viral transmission to calves and ameliorates the impact of enteric and respiratory ailments across all age groups within the herd.This study presents an in silico methodology for devising a multiepitope vaccine targeting BCoV.The spike glycoprotein(S)and nucleocapsid(N)proteins,which are integral elements of the BCoV structure,play pivotal roles in the viral infection cycle and immune response.We constructed a remarkably effective multiepitope vaccine candidate specifically designed to combat the BCoV population.Using immunoinformatics technology,B-cell and T-cell epitopes were predicted and linked together using linkers and adjuvants to efficiently trigger both cellular and humoral immune responses in cattle.The in silico construct was characterized,and assessment of its physicochemical properties revealed the formation of a stable vaccine construct.After 3D modeling of the vaccine construct,molecular docking revealed a stable interaction with the bovine receptor bTLR4.Moreover,the viability of the vaccine’s high expression and simple purification was demonstrated by codon optimization and in silico cloning expression into the pET28a(+)vector.By applying immunoinformatics approaches,researchers aim to better understand the immune response to bovine coronavirus,discover potential targets for intervention,and facilitate the development of diagnostic tools and vaccines to mitigate the impact of this virus on cattle health and the livestock industry.We anticipate that the design will be useful as a preventive treatment for BCoV sickness in cattle,opening the door for further laboratory studies.
文摘Host and viral factors deeply influence the human immunodeficiency virus(HIV) disease progression. Among them human leukocyte antigen(HLA) locus plays a key role at different levels. In fact, genes of the HLA locus have shown the peculiar capability to modulate both innate and adaptive immune responses. In particular, HLA class Ⅰmolecules are recognized by CD8+ T-cells and natural killers(NK) cells towards the interaction with T cell receptor(TCR) and Killer Immunoglobulin Receptor(KIR) 3DL1 respectively. Polymorphisms within the different HLA alleles generate structural changes in HLA classⅠpeptide-binding pockets. Amino acid changes in the peptide-binding pocket lead to the presentation of a different set of peptides to T and NK cells. This review summarizes the role of HLA in HIV progression toward acquired immunodeficiency disease syndrome and its receptors. Recently, many studies have been focused on determining the HLA binding-peptides. The novel use of immune-informatics tools, from the prediction of the HLA-bound peptides to the modification of the HLAreceptor complexes, is considered. A better knowledge of HLA peptide presentation and recognition are allowing new strategies for immune response manipulation to be applied against HIV virus.
基金supported by the BeijingMunicipal Science&Technology Commission(7212103)the Eighth Medical Center of PLA General Hospital(MS202211002).
文摘Background:Diagnosing latent tuberculosis(TB)infection(LTBI)and active TB(ATB)is crucial for preventing disease progression and transmission.However,current diagnostic tests have limitations in terms of accuracy and sensitivity,making it challenging to diagnose these different infection states.Therefore,this study intends to develop a promising biomarker for LTBI and ATB diagnosis to overcome the limitations of the current diagnostic tests.Methods:We developed a novelmultiepitope-based diagnostic biomarker(MEBDB)fromLTBI region of differentiation antigens using bioinformatics and immunoinformatics.Immune responses induced byMEBDM were detected using enzyme-linked immunosorbent spot and cytometric bead assays.This study was conducted from April 2022 to December 2022 in the SeniorDepartment of Tuberculosis at the 8thMedical Center of PLA General Hospital,China.Blood samples were collected from participants with ATB,individuals with LTBI,and healthy controls(HCs).The diagnostic efficacy of MEBDB was evaluated using receiver operating characteristic curves.Results:A novel MEBDB,designated as CP19128P,was generated.CP19128P comprises 19 helper T lymphocyte epitopes,12 cytotoxic T lymphocyte epitopes,and 8 B-cell epitopes.In silico simulations demonstrated that CP19128P possesses strong affinity for Toll-like receptors and elicits robust innate and adaptive immune responses.CP19128P generated significantly higher levels of tumor necrosis factor(TNF-α),interleukin 4(IL-4),and IL-10 in ATB patients(n=7)and LTBI(n=8)individuals compared with HCs(n=62)(P<0.001).Moreover,CP19128P-induced specific cytokines could be used to discriminate LTBI and ATB from healthy subjects with high sensitivity and specificity.Combining IL-2 with IL-4 or TNF-α could differentiate LTBI from HCs(the area under the receiver operating characteristic curve[AUC],0.976[95% confidence interval[CI],0.934-1.000]or 0.986[0.956-1.000]),whereas combining IL-4 with IL-17A or TNF-α could differentiate ATB from HCs(AUC,0.887[0.782-0.993]or 0.984[0.958-1.000]).Conclusions:Our study revealed that CP19128P is a potential MEBDBfor the diagnosis of LTBI andATB.Our findings suggest a promising strategy for developing novel,accurate,and sensitive diagnostic biomarkers and identifying new targets for TB diagnosis and management.
文摘Background:Coronavirus disease 2019(COVID-19)linked with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)cause severe illness and life-threatening pneumonia in humans.The current COVID-19 pandemic demands an effective vaccine to acquire protection against the infection.Therefore,the present study was aimed to design a multiepitope-based subunit vaccine(MESV)against COVID-19.Methods:Structural proteins(Surface glycoprotein,Envelope protein,and Membrane glycoprotein)of SARS-CoV-2 are responsible for its prime functions.Sequences of proteins were downloaded from GenBank and several immunoinformatics coupled with computational approaches were employed to forecast B-and T-cell epitopes from the SARS-CoV-2 highly antigenic structural proteins to design an effective MESV.Results:Predicted epitopes suggested high antigenicity,conserveness,substantial interactions with the human leukocyte antigen(HLA)binding alleles,and collective global population coverage of 88.40%.Taken together,276 amino acids long MESV was designed by connecting 3 cytotoxic T lymphocytes(CTL),6 helper T lymphocyte(HTL)and 4 B-cell epitopes with suitable adjuvant and linkers.The MESV construct was non-allergenic,stable,and highly antigenic.Molecular docking showed a stable and high binding affinity of MESV with human pathogenic toll-like receptors-3(TLR3).Furthermore,in silico immune simulation revealed significant immunogenic response of MESV.Finally,MEV codons were optimized for its in silico cloning into the Escherichia coli K-12 system,to ensure its increased expression.Conclusion:The MESV developed in this study is capable of generating immune response against COVID-19.Therefore,if designed MESV further investigated experimentally,it would be an effective vaccine candidate against SARS-CoV-2 to control and prevent COVID-19.
基金This work was supported by a National Basic Research Program of China(973 Program,No.2014CB745202)the Shenzhen Peacock Team Project(No.KQTD2015033117210153)+1 种基金the Shenzhen Science and Technology Innovation Committee Basic Science Research Grants(No.JCYJ20170413154523577,No.JCYJ20150629151046896)the Guangdong Natural Science Funds for Distinguished Young Scholar Grant(No.S2013050016987).
文摘Cancer immunotherapy has now been conclusively shown to be capable of producing durable responses for a substantial number of patients.Adoptive cell transfer and checkpoint blockade therapies in particular both demonstrate that antigen-specific immune responses can be dramatically effective,even in previously refractory late stage disease.Such developments,together with advances in technology,have strongly encouraged revisiting the concept of neoantigen vaccines.Here we introduce basic ideas in the field to allow investigators from diverse backgrounds to understand these developments,grasp current issues,and contribute to further progress.
