[en] [en] BACKGROUND: Strongyloides stercoralis is a soil-transmitted helminth causing strongyloidiasis, mainly affecting impoverished populations in tropical and subtropical regions. Despite its high global prevalence, affecting an estimated 613.9 million people, it remains neglected in public health initiatives. Current treatments, including albendazole and ivermectin, show variable efficacy and face potential resistance, making vaccine development critical for long-term control and achieving WHO targets.
METHODS: We employed an immunoinformatics approach to design a multi-epitope vaccine candidate by combining B-cell and T-cell epitopes from key L3-stage proteins involved in S. stercoralis infection. In addition, interactions with TLR4 were implemented to assess the vaccine’s ability to elicit an innate immune response.
RESULTS: The selected proteins exhibited strong conservation, suggesting potential cross-protection across Strongyloides strains. The vaccine candidate was predicted to be antigenic, non-allergenic, and immunogenic, with immune simulation demonstrating robust activation of humoral and cellular immune responses. Extensive HLA coverage analysis indicated broad population applicability. Additionally, protein–protein docking and normal-mode analyses indicated efficient binding and stable interaction of the vaccine candidate with TLR4.
CONCLUSION: This study provides a promising approach to designing multi-epitope vaccines against S. stercoralis designed through integrative immunoinformatics. Overall, the designed vaccine candidate demonstrated immunogenicity and safety features that warrant further experimental validation in vitro and in vivo. These findings lay important groundwork for future vaccine development aimed at improving the prevention and control of strongyloidiasis globally.
SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12879-026-12948-w.
Disciplines :
Pharmacy, pharmacology & toxicology
Author, co-author :
Stong Tangan, Yanick Aqua; Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea, Cameroon. tangan.yanick@ubuea.cm
Nchanji, G Takop; Tropical Disease Interventions, Diagnostics, Vaccines, and Therapeutics (TroDDIVaT) Initiative, Frontline Association, Tiko, Cameroon ; Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea, Cameroon
Ndumu, Eric; Centre for Research in Infectious Diseases, CRID-CAM, Yaounde, Cameroon
Ayuk, Abey Blessings; Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea, Cameroon
Ngala, Kongnyu Brandon; Centre for Research in Infectious Diseases, CRID-CAM, Yaounde, Cameroon
Dulandzev, Melvis Berinyuy; Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea, Cameroon
Yaah, Ntang Emmaculate; Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea, Cameroon
Lahngong, Methodius Shinyuy ; Université de Liège - ULiège > Unités de recherche interfacultaires > Centre Interdisciplinaire de Recherche sur le Médicament (CIRM)
Shintouo, Cabirou Mounchili; Department of Microbiology and Immunology, College of Medicine, Drexel University, Philadelphia, PA, USA
Yengo, Bernis Neneyoh; Department of Microbiology and Immunology, College of Medicine, Drexel University, Philadelphia, PA, USA
Enowkpen, Andreen Egbe; Centre for Research in Infectious Diseases, CRID-CAM, Yaounde, Cameroon
Efeti, Mary Teke; Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea, Cameroon ; Frailty in Ageing Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, B-1090, Belgium ; Department of Gerontology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, Brussels, B-1090, Belgium
Chick, Joan Amban; Department of Computer and Information Sciences, College of Science and Technology, Covenant University, Ota, Nigeria
Gwei, Ketura Yaje; Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea, Cameroon
Vanhamme, Luc; Department of Molecular Biology, Institute of Biology and Molecular Medicine, IBMM, Université Libre de Bruxelles, Gosselies, Charleroi, Belgium
Souopgui, Jacob; Department of Molecular Biology, Institute of Biology and Molecular Medicine, IBMM, Université Libre de Bruxelles, Gosselies, Charleroi, Belgium
Ghogomu, Stephen Mbigha; Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea, Cameroon. stephen.ghogomu@ubuea.cm
Shey, Robert Adamu; Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea, Cameroon. sheynce@gmail.com ; Tropical Disease Interventions, Diagnostics, Vaccines, and Therapeutics (TroDDIVaT) Initiative, Frontline Association, Tiko, Cameroon. sheynce@gmail.com
Schar F, et al. Strongyloides stercoralis: global distribution and risk factors. PLoS Negl Trop Dis. 2013;7(7):e2288.
Agrawal V Agarwal T Ghoshal UC Intestinal strongyloidiasis: a diagnosis frequently missed in the tropics Trans R Soc Trop Med Hyg 2009 103 3 242 46 18804829 10.1016/j.trstmh.2008.08.009
Puthiyakunnon S, et al. Strongyloidiasis-an insight into its global prevalence and management. PLoS Negl Trop Dis. 2014;8(8):e3018.
Bethony J et al. Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm Lancet 2006 367 9521 1521 32 16679166 10.1016/S0140-6736(06)68653-4
Gordon CA, et al. Strongyloidiasis. Nat Rev Dis Primers. 2024;10(1):6.
Buonfrate D, et al. The global prevalence of Strongyloides stercoralis infection. Pathogens. 2020;9(6).
Albonico M, et al. Controlling soil-transmitted helminthiasis in pre-school-age children through preventive chemotherapy. PLoS Negl Trop Dis. 2008;2(3):e126.
Olsen A et al. Strongyloidiasis-the most neglected of the neglected tropical diseases? Trans R Soc Trop Med Hyg 2009 103 10 967 72 19328508 10.1016/j.trstmh.2009.02.013
Tiberti N, et al. Systemic profile of immune factors in an elderly Italian population affected by chronic strongyloidiasis. Parasit Vectors, 2020. 13(1):515.
Luvira V, et al. Strongyloides stercoralis: a neglected but fatal parasite. Trop Med Infect Dis. 2022;7(10).
Keiser PB Nutman TB Strongyloides stercoralis in the immunocompromised population Clin Microbiol Rev 2004 17 1 208 17 14726461 321465 10.1128/CMR.17.1.208-217.2004
Montes M, et al. Regulatory T cell expansion in HTLV-1 and strongyloidiasis co-infection is associated with reduced IL-5 responses to Strongyloides stercoralis antigen. PLoS Negl Trop Dis. 2009;3(6):e456.
Horton J. Albendazole: a review of anthelmintic efficacy and safety in humans. Parasitology. 2000;121 Suppl: p.:S113–32.
Ikeda T [Pharmacological effects of ivermectin, an antiparasitic agent for intestinal strongyloidiasis: its mode of action and clinical efficacy] Nihon Yakurigaku Zasshi 2003 122 6 527 38 1:CAS:528:DC%2BD3sXpsFWnsLg%3D 14639007 10.1254/fpj.122.527
Geary TG et al. Unresolved issues in anthelmintic pharmacology for helminthiases of humans Int J Parasitol 2010 40 1 1 13 1:CAS:528:DC%2BD1MXhsFyns7zE 19932111 10.1016/j.ijpara.2009.11.001
Osei-Atweneboana MY, et al. Phenotypic evidence of emerging ivermectin resistance in Onchocerca volvulus. PLoS Negl Trop Dis. 2011;5(3):e998.
Eng JK et al. Ivermectin selection on beta-tubulin: evidence in Onchocerca volvulus and haemonchus contortus Mol Biochem Parasitol 2006 150 2 229 35 1:CAS:528:DC%2BD28XhtFOiurjO 17007942 10.1016/j.molbiopara.2006.08.007
Abraham D et al. Immunization with the recombinant antigen Ss-IR induces protective immunity to infection with Strongyloides stercoralis in mice Vaccine 2011 29 45 8134 40 1:CAS:528:DC%2BC3MXht12jsbvP 21856350 3191285 10.1016/j.vaccine.2011.08.030
Bergquist R Lustigman S Control of important helminthic infections vaccine development as part of the solution Adv Parasitol 2010 73 297 326 20627146 10.1016/S0065-308X(10)73010-4
Shey RA, et al. Computational design and preliminary serological analysis of a novel multi-epitope vaccine candidate against onchocerciasis and related filarial diseases. Pathogens. 2021;10(2).
Bethony J et al. Antibodies against a secreted protein from hookworm larvae reduce the intensity of hookworm infection in humans and vaccinated laboratory animals Faseb J 2005 19 12 1743 45 1:CAS:528:DC%2BD2MXhtFSjtr7J 16037096 10.1096/fj.05-3936fje
Zhan B, et al. Molecular cloning, biochemical characterization, and partial protective immunity of the heme-binding glutathione S-transferases from the human hookworm Necator americanus. Infect Immun, 2010. 78(4):1552–63.
Bethony JM et al. Randomized, placebo-controlled, double-blind trial of the Na-ASP-2 hookworm vaccine in unexposed adults Vaccine 2008 26 19 2408 17 1:CAS:528:DC%2BD1cXls1yktb8%3D 18396361 10.1016/j.vaccine.2008.02.049
Maleki A et al. In silico design of recombinant multi-epitope vaccine against influenza a virus BMC Bioinf 2022 22 Suppl 14 617 10.1186/s12859-022-04581-6
Sanches RCO et al. Immunoinformatics design of multi-epitope peptide-based vaccine against Schistosoma mansoni using transmembrane proteins as a target Front Immunol 2021 12 621706 33737928 7961083 10.3389/fimmu.2021.621706
Pandey RK et al. Immunoinformatics approaches to design a novel multi-epitope subunit vaccine against HIV infection Vaccine 2018 36 17 2262 72 1:CAS:528:DC%2BC1cXlt1Omt7Y%3D 29571972 10.1016/j.vaccine.2018.03.042
Lei Y et al. Enhanced efficacy of a multi-epitope vaccine for type A and O foot‑and-mouth disease virus by fusing multiple epitopes with Mycobacterium tuberculosis heparin-binding hemagglutinin (HBHA), a novel TLR4 agonist 2020 Mol Immunol 118 26 121
Zhou WY et al. Therapeutic efficacy of a multi-epitope vaccine against Helicobacter pylori infection in BALB/c mice model Vaccine 2009 27 36 5013 19 1:CAS:528:DC%2BD1MXos12rtrs%3D 19446591 10.1016/j.vaccine.2009.05.009
Sanami S et al. Design of a multi-epitope vaccine against SARS-CoV-2 using immunoinformatics approach Int J Biol Macromol 2020 164 871 83 1:CAS:528:DC%2BB3cXhsVylu7zP 32682041 7362859 10.1016/j.ijbiomac.2020.07.117
Naderian R, et al. Rational design of multi-epitope vaccine for chandipura virus using an immunoinformatics approach. PLoS One. 2025;20(10):e0335147.
Culma MF Strongyloides stercoralis proteome: a reverse approach to the identification of potential immunogenic candidates 2021 Microb Pathog 104545 152
Sanchez-Palencia LF, et al. Evaluation of the immunomodulatory effect of the recombinant 14-3-3 and Major antigen proteins of Strongyloides stercoralis against an infection by S. venezuelensis. Vaccines (Basel). 2022;10(8).
Tarke A et al. Targets and cross-reactivity of human T cell recognition of common cold coronaviruses Cell Rep. Med 2023 4 6 101088 1:CAS:528:DC%2BB3sXht1KmtrrK 37295422 10242702 10.1016/j.xcrm.2023.101088
Sanchez-Trincado JL, Gomez-Perosanz M, Reche PA. Fundamentals and methods for T- and B-Cell epitope prediction. J Immunol Res 2017. 2017;2680160.
Luo W, Yin Q. B cell response to vaccination. Immunol Invest, 2021. 50(7):780–801.
Clifford JN, et al. BepiPred-3.0: improved B-cell epitope prediction using protein language models. Protein Sci. 2022;31(12):e4497.
Saha S Raghava GP Prediction of continuous B-cell epitopes in an antigen using recurrent neural network Proteins 2006 65 1 40 48 1:CAS:528:DC%2BD28Xpt1Cmurk%3D 16894596 10.1002/prot.21078
Sette A et al. The development of multi-epitope vaccines: epitope identification, vaccine design and clinical evaluation Biologicals 2001 29 3–4 271 76 1:CAS:528:DC%2BD38Xht1Oksrg%3D 11851327 10.1006/biol.2001.0297
Peters B et al. Identifying MHC class I epitopes by predicting the TAP transport efficiency of epitope precursors J Immunol 2003 171 4 1741 49 1:CAS:528:DC%2BD3sXmtVWntrY%3D 12902473 10.4049/jimmunol.171.4.1741
Pedras-Vasconcelos JA Pearce EJ Type 1 CD8+ T cell responses during infection with the helminth Schistosoma mansoni J Immunol 1996 157 7 3046 53 1:CAS:528:DyaK28XlvVWmurs%3D 8816414 10.4049/jimmunol.157.7.3046
Nielsen M Lund O NN-align. An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction BMC Bioinf 2009 10 296 10.1186/1471-2105-10-296
Reynisson B, et al. NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data. Nucleic Acids Res. 2020;48(W1):W449–54.
Doytchinova IA Flower DR VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines BMC Bioinf 2007 8 4 10.1186/1471-2105-8-4
Bui HH et al. Predicting population coverage of T-cell epitope-based diagnostics and vaccines BMC Bioinf 2006 7 153 10.1186/1471-2105-7-153
Dey J, et al. Designing a novel multi-epitope vaccine to evoke a robust immune response against pathogenic multidrug-resistant Enterococcus faecium bacterium. Gut Pathog, 2022. 14(1):21.
Lee SJ, et al. A potential protein adjuvant derived from Mycobacterium tuberculosis Rv0652 enhances dendritic cells-based tumor immunotherapy. PLoS One. 2014;9(8):e104351.
Kerepesi LA et al. Toll-like receptor 4 (TLR4) is required for protective immunity to larval Strongyloides stercoralis in mice Microbes Infect 2007 9 1 28 34 1:CAS:528:DC%2BD2sXhtVejsLo%3D 17196865 10.1016/j.micinf.2006.10.003
Arai R et al. Design of the linkers which effectively separate domains of a bifunctional fusion protein Protein Eng 2001 14 8 529 32 1:CAS:528:DC%2BD3MXns1Giurs%3D 11579220 10.1093/protein/14.8.529
Livingston B et al. A rational strategy to design multiepitope immunogens based on multiple Th lymphocyte epitopes J Immunol 2002 168 11 5499 506 1:CAS:528:DC%2BD38XktFCrs7k%3D 12023344 10.4049/jimmunol.168.11.5499
Alexander J et al. Linear PADRE T helper epitope and carbohydrate B cell epitope conjugates induce specific high titer IgG antibody responses J Immunol 2000 164 3 1625 33 1:CAS:528:DC%2BD3cXot1Kiuw%3D%3D 10640784 10.4049/jimmunol.164.3.1625
Clark E, Nava B, Caputi M. Tat is a multifunctional viral protein that modulates cellular gene expression and functions. Oncotarget, 2017. 8(16):27569–81.
Vives E et al. TAT peptide internalization: seeking the mechanism of entry Curr Protein Pept Sci 2003 4 2 125 32 1:CAS:528:DC%2BD3sXitlSrt7g%3D 12678851 10.2174/1389203033487306
Reddy Chichili VP Kumar V Sivaraman J Linkers in the structural biology of protein-protein interactions Protein Sci 2013 22 2 153 67 1:CAS:528:DC%2BC3sXhsVOnsLc%3D 23225024 3588912 10.1002/pro.2206
Yang Y, et al. In silico design of a DNA-based HIV-1 multi-epitope vaccine for Chinese populations. Hum Vaccin Immunother, 2015. 11(3):795–805.
Yano A et al. An ingenious design for peptide vaccines Vaccine 2005 23 17–18 2322 26 1:CAS:528:DC%2BD2MXitVCgt7Y%3D 15755620 10.1016/j.vaccine.2005.01.031
Chen X Zaro JL Shen WC Fusion protein linkers: property, design and functionality Adv Drug Deliv Rev 2013 65 10 1357 69 1:CAS:528:DC%2BC38XhsFWitbvN 23026637 10.1016/j.addr.2012.09.039
Schoenborn JR Wilson CB Regulation of interferon-gamma during innate and adaptive immune responses Adv Immunol 2007 96 41 101 1:CAS:528:DC%2BD1cXhs1ajtbw%3D 17981204 10.1016/S0065-2776(07)96002-2
Dhanda SK Vir P Raghava GP Designing of interferon-gamma inducing MHC class-II binders Biol Direct 2013 8 30 24304645 4235049 10.1186/1745-6150-8-30
Gupta S et al. Identification of B-cell epitopes in an antigen for inducing specific class of antibodies Biol Direct 2013 8 27 24168386 3831251 10.1186/1745-6150-8-27
Wilkins MR et al. Protein identification and analysis tools in the ExPASy server Methods Mol Biol 1999 112 531 52 1:CAS:528:DyaK1cXotVGrtrg%3D 10027275
Rosano GL Ceccarelli EA Recombinant protein expression in Escherichia coli: advances and challenges Front Microbiol 2014 5 172 24860555 4029002 10.3389/fmicb.2014.00172
Wang C, Zou Q. Prediction of protein solubility based on sequence physicochemical patterns and distributed representation information with DeepSoluE. BMC Biol, 2023. 21(1):p. 12.
Magnan CN et al. High-throughput prediction of protein antigenicity using protein microarray data Bioinformatics 2010 26 23 2936 43 1:CAS:528:DC%2BC3cXhsVKjtL3E 20934990 2982151 10.1093/bioinformatics/btq551
Dimitrov I et al. AllerTOP v.2-a server for in silico prediction of allergens J Mol Model 2014 20 6 2278 24878803 10.1007/s00894-014-2278-5
Dimitrov I et al. AllergenFP: allergenicity prediction by descriptor fingerprints Bioinformatics 2014 30 6 846 51 1:CAS:528:DC%2BC2cXks12jsb4%3D 24167156 10.1093/bioinformatics/btt619
Buchan DWA, Jones DT. The PSIPRED protein analysis workbench: 20 years on. Nucleic Acids Res. 2019;47(W1):W402–07.
MacRaild CA, et al. Disordered epitopes as peptide vaccines. Pept Sci (Hoboken). 2018;110(3):e24067.
Erdos G, Pajkos M, Dosztanyi Z. IUPred3: prediction of protein disorder enhanced with unambiguous experimental annotation and visualization of evolutionary conservation. Nucleic Acids Res. 2021;49(W1):W297–303.
Ishida T, Kinoshita K. PrDOS: prediction of disordered protein regions from amino acid sequence. Nucleic Acids Res. 2007;35(Web Server issue):W460–4.
Patil NA et al. Cellular disulfide bond formation in bioactive peptides and proteins Int J Mol Sci 2015 16 1 1791 805 1:CAS:528:DC%2BC2MXkt1ejtbY%3D 25594871 4307334 10.3390/ijms16011791
Ryan N et al. Immunoinformatics approach for design novel multi-epitope prophylactic and therapeutic vaccine based on capsid proteins L1 and L2 and oncoproteins E6 and E7 of human papillomavirus 16 and human papillomavirus 18 against cervical cancer Osong Public Health Res Perspect 2024 15 4 307 28 39039819 11391375 10.24171/j.phrp.2024.0013
Cheng J Saigo H Baldi P Large-scale prediction of disulphide bridges using kernel methods, two-dimensional recursive neural networks, and weighted graph matching Proteins 2006 62 3 617 29 1:CAS:528:DC%2BD28XhsVGruro%3D 16320312 10.1002/prot.20787
Jumper J et al. Highly accurate protein structure prediction with AlphaFold Nature 2021 596 7873 583 89 1:CAS:528:DC%2BB3MXhvVaktrrL 34265844 8371605 10.1038/s41586-021-03819-2
Mirdita M et al. ColabFold: making protein folding accessible to all Nat Methods 2022 19 6 679 82 1:CAS:528:DC%2BB38XhsVWjsLfL 35637307 9184281 10.1038/s41592-022-01488-1
Heo L, Park H, Seok C. GalaxyRefine: protein structure refinement driven by side-chain repacking. Nucleic Acids Res. 2013;41(Web Server issue):W384–8.
Wiederstein M, Sippl MJ. ProSA-web: interactive web service for the recognition of errors in three-dimensional structures of proteins. Nucleic Acids Res. 2007;35(Web Server issue):W407–10.
Colovos C Yeates TO Verification of protein structures: patterns of nonbonded atomic interactions Protein Sci 1993 2 9 1511 19 1:CAS:528:DyaK2cXhvVKltbk%3D 8401235 2142462 10.1002/pro.5560020916
Barlow DJ Edwards MS Thornton JM Continuous and discontinuous protein antigenic determinants Nature 1986 322 6081 747 48 1:CAS:528:DyaL28XlsFWju7c%3D 2427953 10.1038/322747a0
Sivalingam GN, Shepherd AJ. An analysis of B-cell epitope discontinuity. Mol Immunol, 2012. 51(3–4):304–09.
Ponomarenko J et al. ElliPro: a new structure-based tool for the prediction of antibody epitopes BMC Bioinf 2008 9 514 10.1186/1471-2105-9-514
Hoie MH et al. DiscoTope-3.0: improved B-cell epitope prediction using inverse folding latent representations Front Immunol 2024 15 1322712 38390326 10882062 10.3389/fimmu.2024.1322712
Tian W, et al. Castp 3.0: computed atlas of surface topography of proteins. Nucleic Acids Res. 2018;46(W1):W363–67.
Kozakov D, et al. The ClusPro web server for protein-protein docking. Nat Protoc, 2017. 12(2):255–78.
Larsen MV et al. Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction BMC Bioinf 2007 8 424 10.1186/1471-2105-8-424
Teilum K Olsen JG Kragelund BB Functional aspects of protein flexibility Cell Mol Life Sci 2009 66 14 2231 47 1:CAS:528:DC%2BD1MXot12lsbc%3D 19308324 11115794 10.1007/s00018-009-0014-6
Lopez-Blanco JR, et al. iMODS: internal coordinates normal mode analysis server. Nucleic Acids Res. 2014;42(Web Server issue):W271–6.
Reis M Wernisch L Savva R Unexpected correlations between gene expression and codon usage bias from microarray data for the whole Escherichia coli K-12 genome Nucleic Acids Res 2003 31 23 6976 85 14627830 290265 10.1093/nar/gkg897
Nussinov R Eukaryotic dinucleotide preference rules and their implications for degenerate codon usage J Mol Biol 1981 149 1 125 31 1:CAS:528:DyaL3MXlsVGntL0%3D 6273582 10.1016/0022-2836(81)90264-3
Shey RA et al. In-silico design of a multi-epitope vaccine candidate against onchocerciasis and related filarial diseases Sci Rep 2019 9 1 4409 30867498 6416346 10.1038/s41598-019-40833-x
Rapin N, et al. Computational immunology meets bioinformatics: the use of prediction tools for molecular binding in the simulation of the immune system. PLoS One. 2010;5(4):e9862.
Dishnica K et al. Novel insights into the somatic proteome of Strongyloides stercoralis infective third-stage larvae Parasit Vectors 2023 16 1 45 1:CAS:528:DC%2BB3sXis1agsLk%3D 36721249 9890704 10.1186/s13071-023-05675-7
Marcilla A et al. Proteomic analysis of Strongyloides stercoralis L3 larvae Parasitology 2010 137 10 1577 83 1:CAS:528:DC%2BC3cXptl2hsrY%3D 20388238 10.1017/S0031182010000314
Brindley PJ et al. Antigens from the surface and excretions/secretions of the filariform larva of Strongyloides stercoralis Mol Biochem Parasitol 1988 28 3 171 80 1:CAS:528:DyaL1cXhvVCrsrs%3D 3386679 10.1016/0166-6851(88)90001-1
Ali M et al. Exploring dengue genome to construct a multi-epitope based subunit vaccine by utilizing immunoinformatics approach to battle against dengue infection Sci Rep 2017 7 1 9232 28835708 5569093 10.1038/s41598-017-09199-w
Meza B et al. A novel design of a multi-antigenic, multistage and multi-epitope vaccine against Helicobacter pylori: an in silico approach 2017 Infect Genet Evol 309 17 49
Kyte J Doolittle RF A simple method for displaying the hydropathic character of a protein J Mol Biol 1982 157 1 105 32 1:CAS:528:DyaL38Xks1yjtro%3D 7108955 10.1016/0022-2836(82)90515-0
Ikai A Thermostability and aliphatic index of globular proteins J Biochem 1980 88 6 1895 98 1:CAS:528:DyaL3MXis1CgsA%3D%3D 7462208
Duan T et al. Toll-like receptor signaling and its role in cell-mediated immunity Front Immunol 2022 13 812774 1:CAS:528:DC%2BB38XhtFOkt7%2FN 35309296 8927970 10.3389/fimmu.2022.812774
Venugopal PG, Nutman TB, Semnani RT. Activation and regulation of toll-like receptors (TLRs) by helminth parasites. Immunol Res, 2009. 43(1–3):252–63.
Castiglione F et al. Simulating Epstein-Barr virus infection with C-ImmSim Bioinformatics 2007 23 11 1371 77 1:CAS:528:DC%2BD2sXns1Olu7Y%3D 17341499 10.1093/bioinformatics/btm044
Akhtar H et al. Over expression of a synthetic gene encoding interferon lambda using relative synonymous codon usage bias in Escherichia coli Pak J Pharm Sci 2013 26 6 1181 88 1:CAS:528:DC%2BC2cXhs1Cjs7k%3D 24191324
Hia F Takeuchi O The effects of codon bias and optimality on mRNA and protein regulation Cell Mol Life Sci 2021 78 5 1909 28 1:CAS:528:DC%2BB3cXit1GjsbbK 33128106 10.1007/s00018-020-03685-7
WHO. World Health Organization. Ending NTDs together towards 2030. 2021.
Molyneux DH Savioli L Engels D Neglected tropical diseases: progress towards addressing the chronic pandemic Lancet 2017 389 10066 312 25 27639954 10.1016/S0140-6736(16)30171-4
Herbert DR et al. Immunoaffinity-isolated antigens induce protective immunity against larval Strongyloides stercoralis in mice Exp Parasitol 2002 100 2 112 20 1:CAS:528:DC%2BD38XkslaisLk%3D 12054701 10.1016/S0014-4894(02)00008-5
Hotez PJ, et al. Eliminating the neglected tropical diseases: translational Science and New technologies. PLoS Negl Trop Dis. 2016;10(3):e0003895.
Beaumier CM, et al. New vaccines for neglected parasitic diseases and dengue. Transl Res, 2013. 162(3):144–55.
Hotez PJ et al. Human anthelminthic vaccines: rationale and challenges Vaccine 2016 34 30 3549 55 27171753 10.1016/j.vaccine.2016.03.112
Wong MTJ et al. Soil-transmitted helminthic vaccines: where are we now? Acta Trop 2023 239 106796 1:CAS:528:DC%2BB3sXjvVegsg%3D%3D 36586174 10.1016/j.actatropica.2022.106796
Levenhagen MA Conte H Costa-Cruz JM Current progress toward vaccine and passive immunization approaches for Strongyloides spp 2016 Immunol Lett 17 23 180
Ramanathan R Nutman T Strongyloides stercoralis infection in the immunocompromised host Curr Infect Dis Rep 2008 10 2 105 10 18462583 3401551 10.1007/s11908-008-0019-6
Romero-Cabello R, et al. Hyperinfection with Strongyloides stercoralis. BMJ Case Rep, 2012. 2012.
Vartak A, Sucheck SJ. Recent advances in subunit vaccine carriers. Vaccines (Basel). 2016;4(2).
Huaman MC et al. Gelatin particle indirect agglutination and enzyme-linked immunosorbent assay for diagnosis of strongyloidiasis using Strongyloides venezuelensis antigen Trans R Soc Trop Med Hyg 2003 97 5 535 38 1:CAS:528:DC%2BD2cXns1Gks7Y%3D 15307419 10.1016/S0035-9203(03)80017-2
MacKenzie JR et al. Eosinophils promote allergic disease of the lung by regulating CD4(+) Th2 lymphocyte function J Immunol 2001 167 6 3146 55 1:CAS:528:DC%2BD3MXmvFGit7o%3D 11544300 10.4049/jimmunol.167.6.3146
Kerepesi LA et al. Human immunoglobulin G mediates protective immunity and identifies protective antigens against larval Strongyloides stercoralis in mice The J Infect Dis 2004 189 7 1282 90 1:CAS:528:DC%2BD2cXjsleqsbg%3D 15031798 10.1086/382484
Rajamanickam A, et al. Altered levels of memory T cell subsets and common gammac cytokines in Strongyloides stercoralis infection and partial reversal following anthelmintic treatment. PLoS Negl Trop Dis. 2018;12(5):e0006481.
Rajasekaran S, Anuradha R, Bethunaickan R. TLR specific immune responses against helminth infections. J Parasitol Res, 2017. 2017;6865789.
Ludwig-Portugall I Layland LE Tlrs, Treg, and B cells, an interplay of regulation during helminth infection Front Immunol 2012 3 8 22566894 3342019 10.3389/fimmu.2012.00008
Hernandez HJ Wang Y Stadecker MJ In infection with Schistosoma mansoni, B cells are required for T helper type 2 cell responses but not for granuloma formation J Immunol 1997 158 10 4832 37 1:CAS:528:DyaK2sXjtFKis7s%3D 9144498 10.4049/jimmunol.158.10.4832
Hayashi Y et al. Protective immunity against Brugia malayi infective larvae in mice. I. Parameters of active and passive immunity Am J Trop Med Hyg 1989 41 6 650 56 1:STN:280:DyaK3czmsFWhtw%3D%3D 2641642 10.4269/ajtmh.1989.41.650
Kerepesi LA, et al. Protective immunity to the larval stages of onchocerca volvulus is dependent on Toll-like receptor 4. Infect Immun, 2005. 73(12):8291–97.
Khatoon N Pandey RK Prajapati VK Exploring leishmania secretory proteins to design B and T cell multi-epitope subunit vaccine using immunoinformatics approach Sci Rep 2017 7 1 8285 28811600 5557753 10.1038/s41598-017-08842-w
Patel SG et al. Cell-penetrating peptide sequence and modification dependent uptake and subcellular distribution of green florescent protein in different cell lines Sci Rep 2019 9 1 6298 31000738 6472342 10.1038/s41598-019-42456-8
Backlund CM, et al. Cell-penetrating peptides enhance peptide vaccine accumulation and persistence in lymph nodes to drive immunogenicity. Proc. Natl. Acad. Sci. U. S. A. 2022;119(32):e2204078119.
Curlin G, et al. Integrating safety and efficacy evaluation throughout vaccine research and development. Pediatrics. 2011;127 Suppl 1(Suppl 1): p.:S9–15.
Wu Y, Collier JH. Alpha-helical coiled-coil peptide materials for biomedical applications. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2017;9(2).
Herbert DR, et al. The role of B cells in immunity against larval Strongyloides stercoralis in mice. Parasite Immunol, 2002. 24(2):95–101.
Bonne-Annee S Hess JA Abraham D Innate and adaptive immunity to the nematode Strongyloides stercoralis in a mouse model Immunol Res 2011 51 2–3 205 14 1:CAS:528:DC%2BC3MXhs1OisbjO 22101674 6707741 10.1007/s12026-011-8258-2
