{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T03:45:39Z","timestamp":1789962339189,"version":"4.0.1"},"reference-count":148,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T00:00:00Z","timestamp":1611187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Les\u00a0amis\u00a0des\u00a0Instituts Pasteur\u00a0\u00e0\u00a0Bruxelles","award":["Postdoc Grant awarded to RAS"],"award-info":[{"award-number":["Postdoc Grant awarded to RAS"]}]},{"name":"Belgian Academy of Higher Education and Research - ARES","award":["PRD2013CMRSOUOPGUI awarded to JS"],"award-info":[{"award-number":["PRD2013CMRSOUOPGUI awarded to JS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Onchocerciasis is a skin and eye disease that exerts a heavy socio-economic burden, particularly in sub-Saharan Africa, a region which harbours greater than 96% of either infected or at-risk populations. The elimination plan for the disease is currently challenged by many factors including amongst others; the potential emergence of resistance to the main chemotherapeutic agent, ivermectin (IVM). Novel tools, including preventative and therapeutic vaccines, could provide additional impetus to the disease elimination tool portfolio. Several observations in both humans and animals have provided evidence for the development of both natural and artificial acquired immunity. In this study, immuno-informatics tools were applied to design a filarial-conserved multi-epitope subunit vaccine candidate, (designated Ov-DKR-2) consisting of B-and T-lymphocyte epitopes of eight immunogenic antigens previously assessed in pre-clinical studies. The high-percentage conservation of the selected proteins and epitopes predicted in related nematode parasitic species hints that the generated chimera may be instrumental for cross-protection. Bioinformatics analyses were employed for the prediction, refinement, and validation of the 3D structure of the Ov-DKR-2 chimera. In-silico immune simulation projected significantly high levels of IgG1, T-helper, T-cytotoxic cells, INF-\u03b3, and IL-2 responses. Preliminary immunological analyses revealed that the multi-epitope vaccine candidate reacted with antibodies in sera from both onchocerciasis-infected individuals, endemic normals as well as loiasis-infected persons but not with the control sera from European individuals. These results support the premise for further characterisation of the engineered protein as a vaccine candidate for onchocerciasis.<\/jats:p>","DOI":"10.3390\/pathogens10020099","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T09:49:21Z","timestamp":1611222561000},"page":"99","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Computational Design and Preliminary Serological Analysis of a Novel Multi-Epitope Vaccine Candidate Against Onchocerciasis and Related Filarial Diseases"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0146-3894","authenticated-orcid":false,"given":"Robert Adamu","family":"Shey","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon"},{"name":"Department of Molecular Biology, Institute of Biology and Molecular Medicine, IBMM, Universit\u00e9 Libre de Bruxelles, Gosselies Campus, 6040 Gosselies, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3459-6554","authenticated-orcid":false,"given":"Stephen Mbigha","family":"Ghogomu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cabirou Mounchili","family":"Shintouo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon"},{"name":"Frailty in Ageing Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium"},{"name":"Department of Gerontology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis Nongley","family":"Nkemngo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, Faculty of Science, University of Buea, Buea 99999, Cameroon"},{"name":"Centre for Research in Infectious Diseases (CRID), Department of Parasitology and Medical Entomology, Yaounde BP 13591, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derrick Neba","family":"Nebangwa","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4024-5681","authenticated-orcid":false,"given":"Kevin","family":"Esoh","sequence":"additional","affiliation":[{"name":"Division of Human Genetics, Health Sciences Campus, Department of Pathology, University of Cape Town, Anzio Rd, Observatory, Cape Town 7925, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ntang Emmaculate","family":"Yaah","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muyanui","family":"Manka\u2019aFri","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel Ebai","family":"Nguve","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6597-5974","authenticated-orcid":false,"given":"Roland Akwelle","family":"Ngwese","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferdinand Ngale","family":"Njume","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Science, University of Buea, Buea 99999, Cameroon"},{"name":"Department of Molecular Biology, Institute of Biology and Molecular Medicine, IBMM, Universit\u00e9 Libre de Bruxelles, Gosselies Campus, 6040 Gosselies, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fru Asa","family":"Bertha","sequence":"additional","affiliation":[{"name":"Department of Public Health and Hygiene, Faculty of Health Science, University of Buea, Buea 99999, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lawrence","family":"Ayong","sequence":"additional","affiliation":[{"name":"Malaria Research Unit, Centre Pasteur Cameroon, Yaound\u00e9 Rue 2005, Cameroon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8853-6031","authenticated-orcid":false,"given":"Rose","family":"Njemini","sequence":"additional","affiliation":[{"name":"Frailty in Ageing Research Group, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium"},{"name":"Department of Gerontology, Faculty of Medicine and Pharmacy, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc","family":"Vanhamme","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Biology and Molecular Medicine, IBMM, Universit\u00e9 Libre de Bruxelles, Gosselies Campus, 6040 Gosselies, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1526-4431","authenticated-orcid":false,"given":"Jacob","family":"Souopgui","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Institute of Biology and Molecular Medicine, IBMM, Universit\u00e9 Libre de Bruxelles, Gosselies Campus, 6040 Gosselies, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,1,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"151","DOI":"10.4103\/0974-777X.81692","article-title":"River blindness: An old disease on the brink of elimination and control","volume":"3","author":"Furtado","year":"2011","journal-title":"J. Glob. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Njume, F.N., Ghogomu, S.M., Shey, R.A., Gainkam, L.O.T., Poelvoorde, P., Humblet, P., Kamgno, J., Robert, A., Mutesa, L., and Lelubre, C. (2019). Identification and characterization of the Onchocerca volvulus Excretory Secretory Product Ov28CRP, a putative GM2 activator protein. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007591"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Walker, M., Little, M.P., Wagner, K.S., Soumbey-Alley, E.W., Boatin, B.A., and Bas\u00e1\u00f1ez, M.-G. (2012). Density-Dependent Mortality of the Human Host in Onchocerciasis: Relationships between Microfilarial Load and Excess Mortality. PLoS Negl. Trop. Dis., 6.","DOI":"10.1371\/journal.pntd.0001578"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1179\/000349802125000718","article-title":"Excess mortality associated with blindness in the onchocerciasis focus of the Mbam Valley, Cameroon","volume":"96","author":"Pion","year":"2002","journal-title":"Ann. Trop. Med. Parasitol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1016\/j.pt.2017.11.009","article-title":"Onchocerciasis-Associated Epilepsy, an Additional Reason for Strengthening Onchocerciasis Elimination Programs","volume":"34","author":"Colebunders","year":"2018","journal-title":"Trends Parasitol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Mandro, M., Fodjo, J.N.S., Mukendi, D., Dusabimana, A., Menon, S., Haesendonckx, S., Lokonda, R., Nakato, S., Nyisi, F., and Abhafule, G. (2020). Ivermectin as an adjuvant to anti-epileptic treatment in persons with onchocerciasis-associated epilepsy: A randomized proof-of-concept clinical trial. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0007966"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s40249-018-0452-1","article-title":"High prevalence of epilepsy in onchocerciasis endemic health areas in Democratic Republic of the Congo","volume":"7","author":"Lenaerts","year":"2018","journal-title":"Infect. Dis. Poverty"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s40249-018-0465-9","article-title":"Onchocerca volvulus as a risk factor for developing epilepsy in onchocerciasis endemic regions in the Democratic Republic of Congo: A case control study","volume":"7","author":"Mandro","year":"2018","journal-title":"Infect. Dis. Poverty"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.ijid.2018.10.021","article-title":"High prevalence of epilepsy in an onchocerciasis endemic health zone in the Democratic Republic of the Congo, despite 14 years of community-directed treatment with ivermectin: A mixed-method assessment","volume":"79","author":"Mukendi","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.pt.2017.08.011","article-title":"Onchocerca volvulus: The Road from Basic Biology to a Vaccine","volume":"34","author":"Lustigman","year":"2018","journal-title":"Trends Parasitol."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Ibe, O., Onwujekwe, O., Uzochukwu, B., Ajuba, M., and Okonkwo, P. (2015). Exploring Consumer Perceptions and Economic Burden of Onchocerciasis on Households in Enugu State, South-East Nigeria. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004231"},{"key":"ref_12","first-page":"495","article-title":"Socioeconomic consequences of blinding onchocerciasis in west Africa","volume":"73","author":"Evans","year":"1995","journal-title":"Bull. World Heal. Organ."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.ijpddr.2016.04.002","article-title":"Research for new drugs for elimination of onchocerciasis in Africa","volume":"6","author":"Kuesel","year":"2016","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13071-017-2301-7","article-title":"Important progress towards elimination of onchocerciasis in the West Region of Cameroon","volume":"10","author":"Kamga","year":"2017","journal-title":"Parasites Vectors"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.pt.2011.10.003","article-title":"Elimination of onchocerciasis from Africa: Possible?","volume":"28","author":"MacKenzie","year":"2012","journal-title":"Trends Parasitol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Osei-Atweneboana, M.Y., Awadzi, K., Attah, S.K., Boakye, D.A., Gyapong, J.O., and Prichard, R.K. (2011). Phenotypic Evidence of Emerging Ivermectin Resistance in Onchocerca volvulus. PLoS Negl. Trop. Dis., 5.","DOI":"10.1371\/journal.pntd.0000998"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13071-015-1159-9","article-title":"Required duration of mass ivermectin treatment for onchocerciasis elimination in Africa: A comparative modelling analysis","volume":"8","author":"Stolk","year":"2015","journal-title":"Parasites Vectors"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2044","DOI":"10.1056\/NEJMoa1705026","article-title":"A Test-and-Not-Treat Strategy for Onchocerciasis inLoa loa\u2013Endemic Areas","volume":"377","author":"Kamgno","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13071-019-3290-5","article-title":"Entomological assessment of the transmission following recrudescence of onchocerciasis in the Como\u00e9 Valley, Burkina Faso","volume":"12","author":"Koala","year":"2019","journal-title":"Parasites Vectors"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Shintouo, C.M., Shey, R.A., Nebangwa, D.N., Esoh, K.K., Nkemngo, F.N., Nguve, J.E., Giron, P., Mutesa, L., Vanhamme, L., and Souopgui, J. (2020). In Silico Design and Validation of OvMANE1, a Chimeric Antigen for Human Onchocerciasis Diagnosis. Pathogens, 9.","DOI":"10.3390\/pathogens9060495"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Gunderson, E.L., Vogel, I., Chappell, L., Bulman, C.A., Lim, K.C., Luo, M., Whitman, J.D., Franklin, C., Choi, Y.-J., and Lefoulon, E. (2020). The endosymbiont Wolbachia rebounds following antibiotic treatment. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008623"},{"key":"ref_22","unstructured":"IrishHealth (2018). Onchocerciasis, IrishHealth."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.pt.2015.06.007","article-title":"Diagnostic Tools for Onchocerciasis Elimination Programs","volume":"31","author":"Vlaminck","year":"2015","journal-title":"Trends Parasitol."},{"key":"ref_24","unstructured":"World Health Organization (2020, June 17). COVID-19: WHO Issues Interim Guidance for Implementation of NTD Programmes. Available online: https:\/\/www.who.int\/neglected_diseases\/news\/COVID19-WHO-interim-guidance-implementation-NTD-programmes\/en\/."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"3549","DOI":"10.1016\/j.vaccine.2016.03.112","article-title":"Human anthelminthic vaccines: Rationale and challenges","volume":"34","author":"Hotez","year":"2016","journal-title":"Vaccine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1475-2883-2-2","article-title":"Final report of the Conference on the eradicability of Onchocerciasis","volume":"2","author":"Dadzie","year":"2003","journal-title":"Filaria J."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Hotez, P.J., Pecoul, B., Rijal, S., Boehme, C., Aksoy, S., Malecela, M., Tapia-Conyer, R., and Reeder, J.C. (2016). Eliminating the Neglected Tropical Diseases: Translational Science and New Technologies. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0003895"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/cid\/ciu467","article-title":"Reaching the London Declaration on Neglected Tropical Diseases Goals for Onchocerciasis: An Economic Evaluation of Increasing the Frequency of Ivermectin Treatment in Africa","volume":"59","author":"Turner","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kim, Y.E., Remme, J.H.F., Steinmann, P., Stolk, W.A., Roungou, J.-B., and Tediosi, F. (2015). Control, Elimination, and Eradication of River Blindness: Scenarios, Timelines, and Ivermectin Treatment Needs in Africa. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003777"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kim, Y.E., Sicuri, E., and Tediosi, F. (2015). Financial and Economic Costs of the Elimination and Eradication of Onchocerciasis (River Blindness) in Africa. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0004056"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Hotez, P.J., Bottazzi, M.E., Zhan, B., Makepeace, B.L., Klei, T.R., Abraham, D., Taylor, D.W., and Lustigman, S. (2015). The Onchocerciasis Vaccine for Africa\u2014TOVA\u2014Initiative. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003422"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Turner, H.C., Walker, M., Lustigman, S., Taylor, D.W., and Bas\u00e1\u00f1ez, M.-G. (2015). Human Onchocerciasis: Modelling the Potential Long-term Consequences of a Vaccination Programme. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003938"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1586\/14760584.2015.1059281","article-title":"The case for vaccine development in the strategy to eradicate river blindness (onchocerciasis) from Africa","volume":"14","author":"Makepeace","year":"2015","journal-title":"Expert Rev. Vaccines"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.3389\/fmicb.2017.01475","article-title":"Vaccination with a Paramyosin-Based Multi-Epitope Vaccine Elicits Significant Protective Immunity against Trichinella spiralis Infection in Mice","volume":"8","author":"Gu","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.meegid.2017.02.007","article-title":"A novel design of a multi-antigenic, multistage and multi-epitope vaccine against Helicobacter pylori: An in silico approach","volume":"49","author":"Meza","year":"2017","journal-title":"Infect. Genet. Evol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.compbiolchem.2016.04.006","article-title":"Designing an efficient multi-epitope peptide vaccine against Vibrio cholerae via combined immunoinformatics and protein interaction based approaches","volume":"62","author":"Nezafat","year":"2016","journal-title":"Comput. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1080\/21645515.2015.1094595","article-title":"Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production","volume":"12","author":"Kobe","year":"2016","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"8291","DOI":"10.1128\/IAI.73.12.8291-8297.2005","article-title":"Protective Immunity to the Larval Stages of Onchocerca volvulus Is Dependent on Toll-Like Receptor 4","volume":"73","author":"Kerepesi","year":"2005","journal-title":"Infect. Immun."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"205","DOI":"10.4049\/jimmunol.153.1.205","article-title":"IL-4- and IL-5-dependent protective immunity to Onchocerca volvulus infective larvae in BALB\/cBYJ mice","volume":"153","author":"Lange","year":"1994","journal-title":"J. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1128\/iai.65.7.2846-2851.1997","article-title":"Protective responses against skin-dwelling microfilariae of Onchocerca lienalis in severe combined immunodeficient mice","volume":"65","author":"Folkard","year":"1997","journal-title":"Infect. Immun."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1046\/j.1365-3024.1996.d01-93.x","article-title":"Protective immunity induced by vaccination with Onchocerca volvulus tropomyosin in rodents","volume":"18","author":"Taylor","year":"1996","journal-title":"Parasite Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"4417","DOI":"10.1128\/iai.63.11.4417-4422.1995","article-title":"Onchocerca volvulus larval antigen, OvB20, induces partial protection in a rodent model of onchocerciasis","volume":"63","author":"Taylor","year":"1995","journal-title":"Infect. Immun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/S1471-4922(01)02115-8","article-title":"Towards a vaccine for onchocerciasis","volume":"17","author":"Cook","year":"2001","journal-title":"Trends Parasitol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ijid.2014.03.450","article-title":"Multi-epitope peptide vaccines for human lymphatic filariasis","volume":"21","author":"Madhumathi","year":"2014","journal-title":"Int. J. Infect. Dis."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Gu, Y., Wei, J., Yang, J., Huang, J., Yang, X., and Zhu, X. (2013). Protective Immunity against Trichinella spiralis Infection Induced by a Multi-Epitope Vaccine in a Murine Model. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0077238"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"380","DOI":"10.1111\/sji.12340","article-title":"Chimeric Epitope Vaccine from Multistage Antigens for Lymphatic Filariasis","volume":"82","author":"Anugraha","year":"2015","journal-title":"Scand. J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/S0020-7519(03)00170-X","article-title":"CD4+-dependent immunity to Onchocerca volvulus third-stage larvae in humans and the mouse vaccination model: Common ground and distinctions","volume":"33","author":"Lustigman","year":"2003","journal-title":"Int. J. Parasitol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1905","DOI":"10.1128\/IAI.68.4.1905-1911.2000","article-title":"Immunity to Onchocerciasis: Cells from Putatively Immune Individuals Produce Enhanced Levels of Interleukin-5, Gamma Interferon, and Granulocyte-Macrophage Colony-Stimulating Factor in Response to Onchocerca volvulus Larval and Male Worm Antigens","volume":"68","author":"Turaga","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1111\/j.1365-3024.1995.tb00885.x","article-title":"Roles for both CD+ and CD8+ T cells in protective immunity against Onchocerca lienalis microfilariae in the mouse","volume":"17","author":"Folkard","year":"1995","journal-title":"Parasite Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1128\/IAI.72.2.810-817.2004","article-title":"Immunoglobulin E and Eosinophil-Dependent Protective Immunity to Larval Onchocerca volvulus in Mice Immunized with Irradiated Larvae","volume":"72","author":"Abraham","year":"2004","journal-title":"Infect. Immun."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.ijpara.2014.04.006","article-title":"Vaccines to combat river blindness: Expression, selection and formulation of vaccines against infection with Onchocerca volvulus in a mouse model","volume":"44","author":"Hess","year":"2014","journal-title":"Int. J. Parasitol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"4174","DOI":"10.1128\/IAI.68.7.4174-4179.2000","article-title":"The Abundant Larval Transcript-1 and -2 Genes ofBrugia malayi Encode Stage-Specific Candidate Vaccine Antigens for Filariasis","volume":"68","author":"Gregory","year":"2000","journal-title":"Infect. Immun."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1016\/j.exppara.2007.02.017","article-title":"Brugia malayi: Comparison of protective immune responses induced by Bm-alt-2 DNA, recombinant Bm-ALT-2 protein and prime-boost vaccine regimens in a jird model","volume":"116","author":"Thirugnanam","year":"2007","journal-title":"Exp. Parasitol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/S1471-4922(02)02310-3","article-title":"Future directions for vaccine-related onchocerciasis research","volume":"18","author":"Nutman","year":"2002","journal-title":"Trends Parasitol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"e6185","DOI":"10.7717\/peerj.6185","article-title":"Application of built-in adjuvants for epitope-based vaccines","volume":"6","author":"Lei","year":"2019","journal-title":"PeerJ"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Lee, S.J., Shin, S.J., Lee, M.H., Lee, M.-G., Kang, T.H., Park, W.S., Soh, B.Y., Park, J.H., Shin, Y.K., and Kim, H.W. (2014). A Potential Protein Adjuvant Derived from Mycobacterium tuberculosis Rv0652 Enhances Dendritic Cells-Based Tumor Immunotherapy. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0104351"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-018-19456-1","article-title":"Novel Immunoinformatics Approaches to Design Multi-epitope Subunit Vaccine for Malaria by Investigating Anopheles Salivary Protein","volume":"8","author":"Pandey","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5499","DOI":"10.4049\/jimmunol.168.11.5499","article-title":"A Rational Strategy to Design Multiepitope Immunogens Based on Multiple Th Lymphocyte Epitopes","volume":"168","author":"Livingston","year":"2002","journal-title":"J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1093\/protein\/14.8.529","article-title":"Design of the linkers which effectively separate domains of a bifunctional fusion protein","volume":"14","author":"Arai","year":"2001","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_60","first-page":"1895","article-title":"Thermostability and Aliphatic Index of Globular Proteins","volume":"88","author":"Ikai","year":"1980","journal-title":"J. Biochem."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-09199-w","article-title":"Exploring dengue genome to construct a multi-epitope based subunit vaccine by utilizing immunoinformatics approach to battle against dengue infection","volume":"7","author":"Ali","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1002\/prot.24488","article-title":"Assessment of template-based protein structure predictions in CASP10","volume":"82","author":"Huang","year":"2014","journal-title":"Proteins Struct. Funct. Bioinform."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"W126","DOI":"10.1093\/nar\/gkm219","article-title":"OPTIMIZER: A web server for optimizing the codon usage of DNA sequences","volume":"35","author":"Romeu","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Mitra, A.K., and Mawson, A.R. (2017). Neglected Tropical Diseases: Epidemiology and Global Burden. Trop. Med. Infect. Dis., 2.","DOI":"10.3390\/tropicalmed2030036"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Hotez, P.J., Aksoy, S., Brindley, P.J., and Kamhawi, S. (2020). World neglected tropical diseases day. PLoS Negl. Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0007999"},{"key":"ref_66","first-page":"21","article-title":"Time for T? Immunoinformatics addresses vaccine design for neglected tropical and emerging infectious diseases","volume":"14","author":"Moise","year":"2014","journal-title":"Expert Rev. Vaccines"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/j.1600-065X.2010.00976.x","article-title":"Vaccines to combat the neglected tropical diseases","volume":"239","author":"Bethony","year":"2010","journal-title":"Immunol. Rev."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Martins-Melo, F.R., Carneiro, M., Ramos, A.N., Heukelbach, J., Ribeiro, A.L.P., and Werneck, G.L. (2018). The burden of Neglected Tropical Diseases in Brazil, 1990-2016: A subnational analysis from the Global Burden of Disease Study 2016. PLoS Negl. Trop. Dis., 12.","DOI":"10.1371\/journal.pntd.0006559"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40249-018-0444-1","article-title":"Innovation in neglected tropical disease drug discovery and development","volume":"7","author":"Weng","year":"2018","journal-title":"Infect. Dis. Poverty"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e330","DOI":"10.1016\/S1473-3099(19)30160-4","article-title":"More medicines alone cannot ensure the treatment of neglected tropical diseases","volume":"19","author":"Chami","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.trsl.2013.03.006","article-title":"New vaccines for neglected parasitic diseases and dengue","volume":"162","author":"Beaumier","year":"2013","journal-title":"Transl. Res."},{"key":"ref_72","unstructured":"(2021, January 16). Expanded Special Project for the Elimination of Neglected Tropical Diseases, E. About the NTD Portal. Available online: http:\/\/ntd.afro.who.int\/en\/espen\/about."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/j.1365-3024.2011.01350.x","article-title":"Future prospects and challenges of vaccines against filariasis","volume":"34","author":"Babayan","year":"2012","journal-title":"Parasite Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Makepeace, B.L., Jensen, S.A., Laney, S.J., Nfon, C.K., Njongmeta, L.M., Tanya, V.N., Williams, S.A., Bianco, A.E., and Trees, A. (2009). Immunisation with a Multivalent, Subunit Vaccine Reduces Patent Infection in a Natural Bovine Model of Onchocerciasis during Intense Field Exposure. PLoS Negl. Trop. Dis., 3.","DOI":"10.1371\/journal.pntd.0000544"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1017\/S0022149X00025931","article-title":"Immunity to Onchocerca lienalis microfilariae in mice. II. Effects of sensitization with a range of heterologous species","volume":"59","author":"Townson","year":"1985","journal-title":"J. Helminthol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Vartak, A., and Sucheck, S.J. (2016). Recent Advances in Subunit Vaccine Carriers. Vaccines, 4.","DOI":"10.3390\/vaccines4020012"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1080\/21645515.2015.1061159","article-title":"iVAX: An integrated toolkit for the selection and optimization of antigens and the design of epitope-driven vaccines","volume":"11","author":"Moise","year":"2015","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5013","DOI":"10.1016\/j.vaccine.2009.05.009","article-title":"Therapeutic efficacy of a multi-epitope vaccine against Helicobacter pylori infection in BALB\/c mice model","volume":"27","author":"Zhou","year":"2009","journal-title":"Vaccine"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/j.1365-3024.2006.00917.x","article-title":"Successful vaccination against Onchocerca ochengi infestation in cattle using live Onchocerca volvulus infective larvae","volume":"29","author":"Achukwi","year":"2007","journal-title":"Parasite Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/j.1365-3024.1994.tb00379.x","article-title":"Vaccination against gastrointestinal nematodes of sheep using purified secretory acetylcholinesterase from Trichostrongylus colubriformis\u2014An initial pilot study","volume":"16","author":"Griffiths","year":"1994","journal-title":"Parasite Immunol."},{"key":"ref_81","first-page":"351","article-title":"Onchocerca volvulus: In vitro killing of microfilaria by neutrophils and eosinophils from experimentally infected chimpanzees","volume":"42","author":"Johnson","year":"1991","journal-title":"Trop. Med. Parasitol. Off. Organ Dtsch. Tropenmedizinische Ges. Dtsch. Ges. fur Tech. Zusammenarbeit (GTZ)"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1365-3083.1992.tb01620.x","article-title":"Cell-Mediated and Monoclonal Antibody-Dependent Killing of Onchocerca volvulus Microfilariae*","volume":"36","author":"Titanji","year":"1992","journal-title":"Scand. J. Immunol."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"George, P.J., Hess, J.A., Jain, S., Patton, J.B., Zhan, T., Tricoche, N., Zhan, B., Bottazzi, M.E., Hotez, P.J., and Abraham, D. (2019). Antibody responses against the vaccine antigens Ov-103 and Ov-RAL-2 are associated with protective immunity to Onchocerca volvulus infection in both mice and humans. PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007730"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2017\/6865789","article-title":"TLR Specific Immune Responses against Helminth Infections","volume":"2017","author":"Rajasekaran","year":"2017","journal-title":"J. Parasitol. Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.4049\/jimmunol.175.2.1170","article-title":"Diminished Expression and Function of TLR in Lymphatic Filariasis: A Novel Mechanism of Immune Dysregulation","volume":"175","author":"Babu","year":"2005","journal-title":"J. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Cho-Ngwa, F., Liu, J., and Lustigman, S. (2010). The Onchocerca volvulus Cysteine Proteinase Inhibitor, Ov-CPI-2, Is a Target of Protective Antibody Response That Increases with Age. PLoS Negl. Trop. Dis., 4.","DOI":"10.1371\/journal.pntd.0000800"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/j.ijpara.2014.05.003","article-title":"Vaccination with a genetically modified Brugia malayi cysteine protease inhibitor-2 reduces adult parasite numbers and affects the fertility of female worms following a subcutaneous challenge of Mongolian gerbils (Meriones unguiculatus) with B. malayi infective larvae","volume":"44","author":"Arumugam","year":"2014","journal-title":"Int. J. Parasitol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-08842-w","article-title":"Exploring Leishmania secretory proteins to design B and T cell multi-epitope subunit vaccine using immunoinformatics approach","volume":"7","author":"Khatoon","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1080\/21645515.2015.1012017","article-title":"In silicodesign of a DNA-based HIV-1 multi-epitope vaccine for Chinese populations","volume":"11","author":"Yang","year":"2015","journal-title":"Hum. Vaccines Immunother."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1111\/j.1365-2249.1994.tb06548.x","article-title":"Ivermectin-facilitated immunity in onchocerciasis; activation of parasite-specific Th1-type responses with subclinical Onchocerca volvulus infection","volume":"96","author":"Soboslay","year":"1994","journal-title":"Clin. Exp. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Hess, J.A., Zhan, B., Torigian, A.R., Patton, J.B., Petrovsky, N., Zhan, T., Bottazzi, M.E., Hotez, P.J., Klei, T.R., and Lustigman, S. (2016). The Immunomodulatory Role of Adjuvants in Vaccines Formulated with the Recombinant Antigens Ov-103 and Ov-RAL-2 against Onchocerca volvulus in Mice. PLoS Negl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004797"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"259","DOI":"10.2174\/187153007782794371","article-title":"Protein structure based strategies for antigen discovery and vaccine development against malaria and other pathogens","volume":"7","author":"Corradin","year":"2007","journal-title":"Endocrine, Metab. Immune Disord. Drug Targets"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s00430-002-0159-5","article-title":"Involvement of Toll-like receptor 4 in the embryogenesis of the rodent filaria Litomosoides sigmodontis","volume":"192","author":"Pfarr","year":"2003","journal-title":"Med. Microbiol. Immunol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-40833-x","article-title":"In-silico design of a multi-epitope vaccine candidate against onchocerciasis and related filarial diseases","volume":"9","author":"Shey","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1046\/j.1365-2567.1997.00210.x","article-title":"The diverse expression of immunity in humans at distinct states of Onchocerca volvulus infection","volume":"90","author":"Soboslay","year":"1997","journal-title":"Immunol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1128\/IAI.01328-06","article-title":"Th1 and Th2 Cells Help CD8 T-Cell Responses","volume":"75","author":"Ekkens","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1038\/nm0202-166","article-title":"IL-4-secreting CD4+ T cells are crucial to the development of CD8+ T-cell responses against malaria liver stages","volume":"8","author":"Carvalho","year":"2002","journal-title":"Nat. Med."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/j.1365-2567.2006.02452.x","article-title":"CD4+ Th1 cells promote CD8+ Tc1 cell survival, memory response, tumor localization and therapy by targeted delivery of interleukin 2 via acquired pMHC I complexes","volume":"120","author":"Huang","year":"2007","journal-title":"Immunology"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1093\/infdis\/157.3.536","article-title":"Onchocerciasis and Immunity in Humans: Enhanced T Cell Responsiveness to Parasite Antigen in Putatively Immune Individuals","volume":"157","author":"Ward","year":"1988","journal-title":"J. Infect. Dis."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1093\/infdis\/171.3.652","article-title":"Immunity to onchocerciasis: Putative immune persons produce a Th1-like response to Onchocerca volvulus","volume":"171","author":"Elson","year":"1995","journal-title":"J. Infect. Dis."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1038\/nri2199","article-title":"Protective immune mechanisms in helminth infection","volume":"7","author":"Anthony","year":"2007","journal-title":"Nat. Rev. Immunol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Katawa, G., Layland, L.E., Debrah, A.Y., Von Horn, C., Batsa, L., Kwarteng, A., Arriens, S., Taylor, D.W., Specht, S., and Hoerauf, A. (2015). Hyperreactive Onchocerciasis is Characterized by a Combination of Th17-Th2 Immune Responses and Reduced Regulatory T Cells. PLoS Negl. Trop. Dis., 9.","DOI":"10.1371\/journal.pntd.0003414"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1007\/s00726-013-1526-9","article-title":"Peptides for immunological purposes: Design, strategies and applications","volume":"45","author":"Gori","year":"2013","journal-title":"Amino Acids"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.biotechadv.2011.09.013","article-title":"Bacterial expression systems for recombinant protein production: E. coli and beyond","volume":"30","author":"Chen","year":"2012","journal-title":"Biotechnol. Adv."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"172","DOI":"10.3389\/fmicb.2014.00172","article-title":"Recombinant protein expression in Escherichia coli: Advances and challenges","volume":"5","author":"Rosano","year":"2014","journal-title":"Front. Microbiol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/S1471-4922(01)02211-5","article-title":"Towards a recombinant antigen vaccine against Onchocerca volvulus","volume":"18","author":"Lustigman","year":"2002","journal-title":"Trends Parasitol."},{"key":"ref_107","first-page":"331","article-title":"Onchocerca volvulus: In vitro cytotoxic effects of human neutrophils and serum on third-stage larvae","volume":"45","author":"Johnson","year":"1994","journal-title":"Trop. Med. Parasitol. Off. Organ Dtsch. Tropenmedizinische Ges. Dtsch. Ges. fur Tech. Zusammenarbeit (GTZ)"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/0035-9203(94)90433-2","article-title":"The effect of ivermectin treatment on the antibody response to antigens of Onchocerca volvulus","volume":"88","author":"Gillespie","year":"1994","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Shey, R.A., Ghogomu, S., Njume, F.N., Gainkam, L.O.T., Poelvoorde, P., Mutesa, L., Robert, A., Humblet, P., Munyampundu, J.-P., and Kamgno, J. (2018). Prediction and validation of the structural features of Ov58GPCR, an immunogenic determinant of Onchocerca volvulus. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0202915"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S0014-5793(98)01454-9","article-title":"Bacteriophage lambda surface display of a bacterial biotin acceptor domain reveals the minimal peptide size required for biotinylation","volume":"440","author":"Stolz","year":"1998","journal-title":"FEBS Lett."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1093\/protein\/gzu043","article-title":"Design and characterization of structured protein linkers with differing flexibilities","volume":"27","author":"Klein","year":"2014","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s41587-019-0036-z","article-title":"SignalP 5.0 improves signal peptide predictions using deep neural networks","volume":"37","author":"Armenteros","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2016\/6760830","article-title":"An Introduction to B-Cell Epitope Mapping and In Silico Epitope Prediction","volume":"2016","author":"Potocnakova","year":"2016","journal-title":"J. Immunol. Res."},{"key":"ref_114","first-page":"121","article-title":"PREDICTING FLEXIBLE LENGTH LINEAR B-CELL EPITOPES","volume":"Volume 7","author":"Dobbs","year":"2008","journal-title":"Proceedings of the Computational Systems Bioinformatics"},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Larsen, M.V., Lundegaard, C., Lamberth, K., Buus, S., Lund, O., and Nielsen, M. (2007). Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-424"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2012\/925135","article-title":"CD4+T Cells: Differentiation and Functions","volume":"2012","author":"Luckheeram","year":"2012","journal-title":"Clin. Dev. Immunol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1111\/imm.12889","article-title":"Improved methods for predicting peptide binding affinity to MHC class II molecules","volume":"154","author":"Jensen","year":"2018","journal-title":"Immunology"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"847","DOI":"10.3389\/fimmu.2018.00847","article-title":"Interferon-Gamma at the Crossroads of Tumor Immune Surveillance or Evasion","volume":"9","author":"Castro","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1745-6150-8-30","article-title":"Designing of interferon-gamma inducing MHC class-II binders","volume":"8","author":"Dhanda","year":"2013","journal-title":"Biol. Direct"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Tao, A., and Raz, E. (2015). Antigenicity, Immunogenicity, Allergenicity. Allergy Bioinformatics, Springer.","DOI":"10.1007\/978-94-017-7444-4"},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1093\/bioinformatics\/btq551","article-title":"High-throughput prediction of protein antigenicity using protein microarray data","volume":"26","author":"Magnan","year":"2010","journal-title":"Bioinform."},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Doytchinova, I., and Toseland, C.P. (2007). VaxiJen: A server for prediction of protective antigens, tumour antigens and subunit vaccines. BMC Bioinform., 8.","DOI":"10.1186\/1471-2105-8-4"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00894-014-2278-5","article-title":"AllerTOP v.2\u2014A server for in silico prediction of allergens","volume":"20","author":"Dimitrov","year":"2014","journal-title":"J. Mol. Model."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1093\/bioinformatics\/btt619","article-title":"AllergenFP: Allergenicity prediction by descriptor fingerprints","volume":"30","author":"Dimitrov","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_125","doi-asserted-by":"crossref","unstructured":"Walker, J.M. (2005). Protein Identification and Analysis Tools on the ExPASy Server. The Proteomics Protocols Handbook, Humana Press.","DOI":"10.1385\/1592598900"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"W402","DOI":"10.1093\/nar\/gkz297","article-title":"The PSIPRED Protein Analysis Workbench: 20 years on","volume":"47","author":"Jones","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_127","doi-asserted-by":"crossref","unstructured":"Shiwang, L., Peng, J., Ma, J., and Xu, J. (2016). Protein Secondary Structure Prediction Using Deep Convolutional Neural Fields. Sci. Rep., 6.","DOI":"10.1038\/srep18962"},{"key":"ref_128","first-page":"482","article-title":"Sixty-five years of the long march in protein secondary structure prediction: The final stretch?","volume":"19","author":"Yang","year":"2016","journal-title":"Briefings Bioinform."},{"key":"ref_129","doi-asserted-by":"crossref","unstructured":"Guy, A.J., Irani, V., MacRaild, C.A., Anders, R.F., Norton, R.S., Beeson, J.G., Richards, J.S., and Ramsland, P.A. (2015). Insights into the Immunological Properties of Intrinsically Disordered Malaria Proteins Using Proteome Scale Predictions. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0141729"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"3433","DOI":"10.1093\/bioinformatics\/bti541","article-title":"IUPred: Web server for the prediction of intrinsically unstructured regions of proteins based on estimated energy content","volume":"21","author":"Csizmok","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/S0076-6879(04)83004-0","article-title":"Protein Structure Prediction Using Rosetta","volume":"Volume 383","author":"Rohl","year":"2004","journal-title":"Methods in Enzymology"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1073\/pnas.1914677117","article-title":"Improved protein structure prediction using predicted interresidue orientations","volume":"117","author":"Yang","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"W406","DOI":"10.1093\/nar\/gkw336","article-title":"3Drefine: An interactive web server for efficient protein structure refinement","volume":"44","author":"Bhattacharya","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"W384","DOI":"10.1093\/nar\/gkt458","article-title":"GalaxyRefine: Protein structure refinement driven by side-chain repacking","volume":"41","author":"Heo","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"W451","DOI":"10.1093\/nar\/gkz288","article-title":"GalaxyRefine2: Simultaneous refinement of inaccurate local regions and overall protein structure","volume":"47","author":"Lee","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_136","doi-asserted-by":"crossref","unstructured":"Haddad, Y., Adam, V., and Heger, Z. (2020). Ten quick tips for homology modeling of high-resolution protein 3D structures. PLoS Comput. Biol., 16.","DOI":"10.1371\/journal.pcbi.1007449"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1002\/pro.2007","article-title":"Protein structure validation by generalized linear model root-mean-square deviation prediction","volume":"21","author":"Bagaria","year":"2011","journal-title":"Protein Sci."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"W407","DOI":"10.1093\/nar\/gkm290","article-title":"ProSA-web: Interactive web service for the recognition of errors in three-dimensional structures of proteins","volume":"35","author":"Wiederstein","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1002\/pro.5560020916","article-title":"Verification of protein structures: Patterns of nonbonded atomic interactions","volume":"2","author":"Colovos","year":"1993","journal-title":"Protein Sci."},{"key":"ref_140","first-page":"747","article-title":"Continuous and discontinuous protein antigenic determinants","volume":"322","author":"Barlow","year":"1986","journal-title":"Nat. Cell Biol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1006\/meth.1996.0054","article-title":"Mapping Epitope Structure and Activity: From One-Dimensional Prediction to Four-Dimensional Description of Antigenic Specificity","volume":"9","year":"1996","journal-title":"Methods"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Ponomarenko, J.V., Bui, H.-H., Li, W., Fusseder, N., Bourne, P.E., Sette, A., and Peters, B. (2008). ElliPro: A new structure-based tool for the prediction of antibody epitopes. BMC Bioinform., 9.","DOI":"10.1186\/1471-2105-9-514"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"3352","DOI":"10.1093\/nar\/gkg512","article-title":"CASTp: Computed Atlas of Surface Topography of proteins","volume":"31","author":"Binkowski","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1093\/bioinformatics\/btp447","article-title":"FRODOCK: A new approach for fast rotational protein\u2013protein docking","volume":"25","author":"Garzon","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Rapin, N., Lund, O., Bernaschi, M., and Castiglione, F. (2010). Computational Immunology Meets Bioinformatics: The Use of Prediction Tools for Molecular Binding in the Simulation of the Immune System. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009862"},{"key":"ref_146","unstructured":"(2020, June 17). Available online: https:\/\/www.riverblindnessvaccinetova.org\/#:~:text=2020%20vision%20of%20a%20vaccine%20against%20river%20blindness&text=The%20International%20Community%20has%20set,public%20health%20problem%20by%202025."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.gene.2016.02.047","article-title":"Synonymous codon usage pattern in glycoprotein gene of rabies virus","volume":"584","author":"Morla","year":"2016","journal-title":"Gene"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1263\/jbb.99.303","article-title":"Solubilization and refolding of bacterial inclusion body proteins","volume":"99","author":"Singh","year":"2005","journal-title":"J. Biosci. Bioeng."}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/2\/99\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:13:34Z","timestamp":1760159614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/10\/2\/99"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,21]]},"references-count":148,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["pathogens10020099"],"URL":"https:\/\/doi.org\/10.3390\/pathogens10020099","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,21]]}}}