Acinetobacter baumannii rOmpA vaccine dose alters immune polarization and immunodominant epitopes

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 mu g vs. 3 mu g). The 3 mu g dose induced a balanced IFN-gamma-IL-4 immune response while the 100 mu g dose induced a polarized IL-4/Type 2 response. Epitope mapping revealed distinct T cell epitopes that activated IFN-gamma-, IL-4-, and IL-17-producing splenocytes. Vaccination with the 100 mu g dose caused epitope spreading among IL-4-producing splenocytes, while it induced fewer reactive epitopes among IFN-gamma-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-gamma-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. (C) 2012 Elsevier Ltd. All rights reserved.