rdf-syntax-grammar
mods:
  schema location: http://www.loc.gov/mods/v3 http://www.loc.gov/standards/mods/v3/mods-3-2.xsd
  title info:
    title: Identification and Evaluation of Brucella Recombinant Outer Membrane Proteins as Subunit Vaccinogen Candidates in the Mouse Model of Brucellosis
  name:
    name part: Gómez, Gabriel
    role:
      role term: creator
    role:
      role term: author.
  name:
    name part: Ficht, Thomas
    role:
      role term: thesis advisor.
  name:
    name part: Adams, Leslie
    role:
      role term: thesis advisor.
  name:
    name part: Texas A & M University
    role:
      role term: degree granting institution.
  type of resource: text
  genre: bibliography
  origin info:
    place:
      place term: txu
    date issued: 2013
    issuance: monographic
  language:
    language term: eng
  physical description:
    form: remote
    extent: 1 online resource.
  abstract: Despite being amongst the most common zoonotic diseases in the world, brucellosis is a neglected disease for which an approved vaccine for human use does not exist. Thus far, the traditional approaches to Brucella antigen selection for subunit vaccine development have yielded unacceptable results. In this work, we evaluated the predictive ability of a multistep Brucella antigen selection process with in vitro immunological and invasion assays and in vivo protection experiments. Initial in silico screening for antigens was performed via genomic sequence analysis where 27 Brucella melitensis open reading frames (ORF) coding for outer membrane proteins bearing MHC epitopes, adhesin and conserved properties were identified. Evidence for a role in any aspect of Brucella virulence (i.e., invasion, co-regulation/expression with known Brucella virulence factors, intracellular adaptation) was then used to narrow the list of candidate antigens. To further increase confidence in the candidate ORF putative role in Brucella pathogenesis, differential expression of candidate ORF was evaluated using previously generated global transcriptomics data in in vitro HeLa and in vivo bovine models of acute Brucella infection. Protein expression in the E. coli heterologous system resulted in the successful expression of OmpW, BtuB, Omp22, Hia, and FlgK. With regards to virulence, the two proteins with the highest predicted adhesin scores conferred an invasive phenotype to the non-invasive BL-21 E. coli strain in alveolar epithelial cells. From an immunogenicity standpoint, all proteins elicited IgG production in Brucella-exposed goats, mouse and humans. Antigen-specific recall responses in splenocytes from C57BL/6 mice immunized with a cocktail of the three proteins with highest MHC scores revealed a mixed Th1/Th2 response with a comparatively greater Th1 response. In protection studies, subcutaneous (SQ) immunization with BtuB, Hia and FlgK, individually, promoted bacterial clearance foll…
  note: by Gabriel Gomez.
  note: "Major Subject: Veterinary Pathology"
  note: Includes vita.
  note: Doctor of Philosophy Texas A & M University 2013 http://hdl.handle.net/1969.1/149282
  note: Includes bibliographical references.
  note: Text (Dissertation)
  subject:
    topic: Major Veterinary Pathology
  subject:
    topic: Brucella
  subject:
    topic: outer membrane proteins
  subject:
    topic: vaccine
  subject:
    topic: antigens
  subject:
    topic: reverse vaccinology
  subject:
    topic: mouse
  identifier: http://hdl.handle.net/1969.1/149282
  record info:
    record content source: TXA
    record creation date: 140129
    record change date: 20151206091638.0
    record identifier: in00003426837
    language of cataloging:
      language term: eng