title: Acinetobacter baumannii rOmpA vaccine dose alters immune polarization and immunodominant epitopes.
abstract: BACKGROUND
  The rOmpA vaccine has been shown to protect mice from lethal infection caused by extreme-drug-resistant (XDR) Acinetobacter baumannii. The role of dose in immunology of the rOmpA vaccine was explored.
  
  
  METHODS
  Mice were vaccinated with various doses of rOmpA plus aluminum hydroxide (Al(OH)(3)) adjuvant. The impact of dose on antibody titers, cytokine production, and immunodominant epitopes was defined.
  
  
  RESULTS
  Anti-rOmpA IgG and IgG subtype titers were higher at larger vaccine doses (30 and 100 μg vs. 3 μg). The 3 μg dose induced a balanced IFN-γ-IL-4 immune response while the 100 μg dose induced a polarized IL-4/Type 2 response. Epitope mapping revealed distinct T cell epitopes that activated IFN-γ-, IL-4-, and IL-17-producing splenocytes. Vaccination with the 100 μg dose caused epitope spreading among IL-4-producing splenocytes, while it induced fewer reactive epitopes among IFN-γ-producing splenocytes.
  
  
  CONCLUSIONS
  Vaccine dose escalation resulted in an enhanced Type 2 immune response, accompanied by substantial IL-4-inducing T cell epitope spreading and restricted IFN-γ-inducing epitopes. These results inform continued development of the rOmpA vaccine against A. baumannii, and also are of general importance in that they indicate that immune polarization and epitope selectivity can be modulated by altering vaccine dose.
authors.affiliation: Division of General Internal Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles Medical Center, Torrance, CA 90502, United States.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.forename: Brandon
authors.initials: B
authors.lastname: Tan
authors.forename: Paul
authors.initials: P
authors.lastname: Pantapalangkoor
authors.forename: Tiffany
authors.initials: T
authors.lastname: Ho
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Hujer
authors.forename: Magdalena A
authors.initials: MA
authors.lastname: Taracila
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
authors.forename: Brad
authors.initials: B
authors.lastname: Spellberg
mesh_terms: D040981:Acinetobacter baumannii / Q000276:immunology*; D000276:Adjuvants, Immunologic; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D018985:Epitopes, B-Lymphocyte / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D016056:Immunodominant Epitopes / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D015847:Interleukin-4 / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D020381:Interleukin-17; C078167:OMPA outer membrane proteins; D015847:Interleukin-4; D007371:Interferon-gamma