Review
Copyright ©The Author(s) 2025.
World J Hepatol. Jul 27, 2025; 17(7): 107620
Published online Jul 27, 2025. doi: 10.4254/wjh.v17.i7.107620
Table 1 Web servers available for predicting Cytotoxic T Lymphocyte, Helper T lymphocyte, and B-cell epitopes
Web server
Prediction methods
Website link
Ref.
Cytotoxic T lymphocyte epitope
NetCTL 1.2Uses an ANN approach to combine MHC class I peptide binding, proteasomal C-terminal cleavage, and TAP transport efficiencyhttps://services.healthtech.dtu.dk/services/NetCTL-1.2/Larsen et al[69], 2007
NetMHCpan 4.1Predicts peptide binding to MHC molecules based on quantitative binding affinity and eluted ligands identified by mass spectrometry, using an ANN approachhttps://services.healthtech.dtu.dk/services/NetMHCpan-4.1/Reynisson et al[70], 2020
CTLPredPredicts CTL epitopes based on T cell epitope patterns, utilizing both ANN and SVM approacheshttp://crdd.osdd.net/raghava/ctlpred/Bhasin and Raghava[71], 2004
Helper T lymphocyte epitope
NetMHCIIpan 4.0Predicts peptide binding to MHC II molecules (HLA-DR, HLA-DQ, HLA-DP) based on binding affinity and eluted ligands identified by mass spectrometry, using an ANN approachhttps://services.healthtech.dtu.dk/services/NetMHCIIpan-4.0/Reynisson et al[70], 2020
ProPredPredicts MHC Class II (HLA-DR) binding regions within antigen sequences using QMhttp://crdd.osdd.net/raghava/propred/Singh and Raghava[72], 2001
MARIAPredicts the likelihood of antigen presentation from a specific gene related to HLA class II alleles, using peptide sequences from mass spectrometry, antigen gene expression levels, and protease cleavage patterns with an ANN approachhttps://maria.stanford.edu/Chen et al[73], 2019
Linear B Cell epitope
ABCpredUses an RNN approach that considers peptide length to predict B cell epitopes within antigen sequenceshttp://crdd.osdd.net/raghava/abcpred/Saha and Raghava[114], 2006
Bepipred Linear Epitope Prediction 2.0Uses a random forest algorithm trained on annotated epitopes from antibody-antigen protein structureshttps://services.healthtech.dtu.dk/services/BepiPred-2.0/Jespersen et al[115], 2017
BCEPSPredicts linear B cell epitopes using an SVM approach based on the tertiary structure of antibody-antigen complexeshttp://imbio.med.ucm.es/bceps/Ras-Carmona et al[116], 2021
SEMAApplies a transfer learning approach using a pre-trained deep learning model to predict conformational B cell epitopes based on primary antigen sequences and tertiary structureshttps://sema.airi.net/Shashkova et al[117], 2022
LBtopeUses SVM and Ibk approaches on a large dataset of experimentally validated B cell epitopes and non-epitopes to predict linear B cell epitopeshttps://webs.iiitd.edu.in/raghava/lbtope/index.phpSingh et al[118], 2013
BcepredPredicts B cell epitopes using physicochemical properties, such as hydrophilicity, flexibility, accessibility, polarity, exposed surface, and turnshttp://crdd.osdd.net/raghava/bcepred/Saha and Raghava[77], 2004
COBEproUses an SVM to predict short peptide fragments within query antigen sequences, calculating an epitope propensity score for each residuehttps://scratch.proteomics.ics.uci.edu/Sweredoski and Baldi[119], 2009
CLBTopeCombines alignment-based and alignment-free machine learning methods to predict B cell epitopes, using epitope and non-epitope sequence compositionhttps://webs.iiitd.edu.in/raghava/clbtope/Kumar et al[120], 2024
Table 2 Web servers available for epitope selection
Parameter
Web server
Accuracy (%)
Link
Ref.
AntigenicityVaxijen v.2.070-89https://www.ddg-pharmfac.net/vaxijen/VaxiJen/VaxiJen.htmlDoytchinova and Flower[121], 2007
Antigenic78.04-80.03http://77.68.43.135:8080/Antigenic/Rahman et al[122], 2019
ANTIGENpro76http://scratch.proteomics.ics.uci.edu/Magnan et al[123], 2010
ToxicityToxinPred3.093https://webs.iiitd.edu.in/raghava/toxinpred3/prediction.phpRathore et al[124], 2024
ToxDL83-90http://www.csbio.sjtu.edu.cn/bioinf/ToxDL/Pan et al[125], 2021
ToxIBTL96http://server.wei-group.net/ToxIBTLWei et al[126], 2022
ImmunogenicityIEDB Immunogenicity66http://tools.iedb.org/immunogenicity/Calis et al[127], 2013
AbImmPred
72.73https://www.genscript.com/tools/antibody-immunogenicityWang et al[128], 2024
DeepImmuno80-90https://deepimmuno.herokuapp.com/Li et al[129], 2021
AllergenicityAllergenFP v.1.088https://www.ddg-pharmfac.net/AllergenFP/index.htmlDimitrov et al[130], 2014
AllerTOP v.285.3https://www.ddg-pharmfac.net/AllerTOP/Dimitrov et al[131], 2014
AllerCatPro 2.084.7https://allercatpro.bii.a-star.edu.sg/Nguyen et al[132], 2022
Population coverageIEDB Population CoverageN/Ahttp://tools.iedb.org/population/Bui et al[133], 2006
AutoimunitymiPepBaseN/Ahttp://proteininformatics.org/mkumar/mipepbase/index.htmlGarg et al[134], 2017
Anti-inflammatoryAIPpred73.4http://211.239.150.230/AIPpred/AIPpredMethod.htmlManavalan et al[135], 2018
PreAIP76.7http://kurata14.bio.kyutech.ac.jp/PreAIP/Khatun et al[136], 2019
PepNet95http://liulab.top/PepNet/serverHan et al[137], 2024
IFN-γ inductionIFNepitope82.1https://webs.iiitd.edu.in/raghava/ifnepitope/run_submit-old.phpDhanda et al[138], 2013
PIP-EL74.8http://www.thegleelab.org/PIP-EL/Manavalan et al[139], 2018
Table 3 Applications of immunoinformatics in chronic hepatitis B therapeutic vaccine design
Targeted antigens
Data type
Data source
Immunoinformatics applications
Ref.
HBV PolymeraseProteomicsNCBIConsensus sequence formation, epitope prediction, epitope selection (based on immunogenicity, toxicity, and conservation), population coverage calculation, and molecular docking analysisZheng et al[96], 2017
HBV polymerase; HBxProteomicsHBVdbEpitope prediction and epitope selection (based on conservation and immunogenicity)de Beijer et al[98], 2020
HBV polymeraseProteomicsNCBIConsensus sequence formation, epitope prediction, epitope selection (antigenicity, allergenicity, toxicity), population coverage calculation, physicochemical property prediction of vaccine candidates, secondary and tertiary structure prediction, molecular docking analysis, and molecular dynamics simulationAhmed et al[100], 2021
HBc; HBxProteomicsNCBIEpitope prediction and epitope selection (conservation and autoimmunity)Saeed et al[101], 2023
LHBsProteomicsNCBIEpitope prediction, physicochemical property prediction, vaccine candidate antigenicity and allergenicity analysis, molecular docking analysis, molecular dynamics simulation, and immune response simulationZhu et al[104], 2024