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@ARTICLE{Srivastava:602306,
      author       = {Srivastava, Sukrit and Kolbe, Michael},
      title        = {{N}ovel “{G}a{E}l {A}ntigenic {P}atches” {I}dentified
                      by a “{R}everse {E}pitomics” {A}pproach to {D}esign
                      {M}ultipatch {V}accines against {NIPAH} {I}nfection, a
                      {S}ilent {T}hreat to {G}lobal {H}uman {H}ealth},
      journal      = {ACS omega},
      volume       = {8},
      number       = {35},
      issn         = {2470-1343},
      address      = {Washington, DC},
      publisher    = {ACS Publications},
      reportid     = {PUBDB-2024-00581},
      pages        = {31698 - 31713},
      year         = {2023},
      abstract     = {Nipah virus (NiV) is a zoonotic virus that causes lethal
                      encephalitis and respiratory disease with the symptom of
                      endothelial cell–cell fusion. Several NiV outbreaks have
                      been reported since 1999 with nearly annual occurrences in
                      Bangladesh. The outbreaks had high mortality rates ranging
                      from 40 to $90\%.$ No specific vaccine has yet been reported
                      against NiV. Recently, several vaccine candidates and
                      different designs of vaccines composed of epitopes against
                      NiV were proposed. Most of the vaccines target single
                      protein or protein complex subunits of the pathogen. The
                      multiepitope vaccines proposed also cover a largely limited
                      number of epitopes, and hence, their efficiency is still
                      uncertain. To address the urgent need for a specific and
                      effective vaccine against NiV infection, in the present
                      study, we have utilized the “reverse epitomics” approach
                      (“overlapping-epitope-clusters-to-patches” method) to
                      identify “antigenic patches” (Ag-Patches) and utilize
                      them as immunogenic composition for multipatch vaccine (MPV)
                      design. The designed MPVs were analyzed for immunologically
                      crucial parameters, physiochemical properties, and
                      interaction with Toll-like receptor 3 ectodomain. In total,
                      30 CTL (cytotoxic T lymphocyte) and 27 HTL (helper T
                      lymphocyte) antigenic patches were identified from the
                      entire NiV proteome based on the clusters of overlapping
                      epitopes. These identified Ag-Patches cover a total of
                      discrete 362 CTL and 414 HTL epitopes from the entire
                      proteome of NiV. The antigenic patches were utilized as
                      immunogenic composition for the design of two CTL and two
                      HTL multipatch vaccines. The 57 antigenic patches utilized
                      here cover 776 overlapping epitopes targeting 52 different
                      HLA class I and II alleles, providing a global ethnically
                      distributed human population coverage of $99.71\%.$ Such
                      large number of epitope coverage resulting in large human
                      population coverage cannot be reached with
                      single-protein/subunit or multiepitope based vaccines. The
                      reported antigenic patches also provide potential
                      immunogenic composition for early detection diagnostic kits
                      for NiV infection. Further, all the MPVs and Toll-like
                      receptor ectodomain complexes show a stable nature of
                      molecular interaction with numerous hydrogen bonds, salt
                      bridges, and nonbounded contact formation and acceptable
                      root mean square deviation and fluctuation. The cDNA
                      analysis shows a favorable large-scale expression of the MPV
                      constructs in a human cell line. By utilizing the novel
                      “reverse epitomics” approach, highly immunogenic novel
                      “GaEl antigenic patches” (GaEl Ag-Patches), a synonym
                      term for “antigenic patches”, were identified and
                      utilized as immunogenic composition to design four MPVs
                      against NiV. We conclude that the novel multipatch vaccines
                      are potential candidates to combat NiV, with greater
                      effectiveness, high specificity, and large human population
                      coverage worldwide.},
      cin          = {CSSB-HZI-MK},
      ddc          = {660},
      cid          = {I:(DE-H253)CSSB-HZI-MK-20210520},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      experiment   = {EXP:(DE-MLZ)NOSPEC-20140101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37692250},
      UT           = {WOS:001052743900001},
      doi          = {10.1021/acsomega.3c01909},
      url          = {https://bib-pubdb1.desy.de/record/602306},
}