PMID- 30790057 OWN - NLM STAT- MEDLINE DCOM- 20190422 LR - 20200516 IS - 1432-1831 (Electronic) IS - 0300-8584 (Linking) VI - 208 IP - 2 DP - 2019 Apr TI - Conserved peptide vaccine candidates containing multiple Ebola nucleoprotein epitopes display interactions with diverse HLA molecules. PG - 227-238 LID - 10.1007/s00430-019-00584-y [doi] AB - Immunoinformatics has come by leaps and bounds to finding potent vaccine candidates against various pathogens. In the current study, a combination of different T (CD4(+) and CD8(+)) and B cell epitope prediction tools was applied to find peptides containing multiple epitopes against Ebola nucleoprotein (NP) and the presentation of peptides to human leukocyte antigen (HLA) molecules was analyzed by prediction, docking and population coverage tools. Further, potential peptides were analyzed by ELISA for peptide induced IFN-gamma secretion in peripheral blood mononuclear cells isolated from healthy volunteers. Six peptides were obtained after merging the overlapping multiple HLA I (CD8(+)) and II (CD4(+)) restricted T cell epitopes as well as B cell epitopes and eliminating the peptides liable to generate autoimmune and allergic response. All peptides displayed 100% conservancy in Zaire ebolavirus. In other Ebola virus species (Sudan, Bundibugyo and Tai forest) and Filoviridae members (Lloviuvirus and Margburgvirus), some peptides were found to be conserved with minor variations. Prediction tools confirmed the ability of predicted peptides to bind with diverse HLA (HLA-A, HLA-B, HLA-DP, HLA-DQ and HLA-DR) alleles. CABS-dock results displayed that the average root mean square deviation (RMSD) value was less than three in majority of cases representing strong binding affinity with HLA alleles. Population coverage analysis predicted high coverage (> 85%) for expected immune response in four continents (Africa, America, Asia and Europe). Nine out of ten blood samples exhibited enhanced IFN-gamma secretion for two peptides (P2 and P3). Thus, the identified NP peptides can be considered as potential synthetic vaccine candidates against Ebola virus. FAU - Jain, Sahil AU - Jain S AD - Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, 147004, India. FAU - Baranwal, Manoj AU - Baranwal M AUID- ORCID: 0000-0002-6581-9346 AD - Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala, Punjab, 147004, India. manoj.baranwal@thapar.edu. LA - eng GR - NA/This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors./ PT - Journal Article DEP - 20190221 PL - Germany TA - Med Microbiol Immunol JT - Medical microbiology and immunology JID - 0314524 RN - 0 (Antigens, Viral) RN - 0 (Ebola Vaccines) RN - 0 (Epitopes) RN - 0 (HLA Antigens) RN - 0 (Nucleoproteins) RN - 0 (Vaccines, Subunit) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Antigens, Viral/genetics/immunology MH - Computational Biology MH - Ebola Vaccines/genetics/*immunology MH - Ebolavirus/genetics/*immunology MH - Epitopes/genetics/*immunology MH - HLA Antigens/genetics/*metabolism MH - Healthy Volunteers MH - Hemorrhagic Fever, Ebola/*prevention & control MH - Humans MH - Interferon-gamma/metabolism MH - Leukocytes, Mononuclear/*immunology MH - Nucleoproteins/genetics/*immunology MH - Vaccines, Subunit/genetics/immunology OTO - NOTNLM OT - Conservation analysis OT - Ebola nucleoprotein OT - Epitope-based vaccine OT - HLA alleles OT - Molecular docking EDAT- 2019/02/23 06:00 MHDA- 2019/04/23 06:00 CRDT- 2019/02/22 06:00 PHST- 2018/09/18 00:00 [received] PHST- 2019/02/11 00:00 [accepted] PHST- 2019/02/23 06:00 [pubmed] PHST- 2019/04/23 06:00 [medline] PHST- 2019/02/22 06:00 [entrez] AID - 10.1007/s00430-019-00584-y [pii] AID - 10.1007/s00430-019-00584-y [doi] PST - ppublish SO - Med Microbiol Immunol. 2019 Apr;208(2):227-238. doi: 10.1007/s00430-019-00584-y. Epub 2019 Feb 21.