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Acinetobacter baumannii rOmpA vaccine dose alters immune polarization and immunodominant epitopes
Lin Lin1, Brandon Tan, Paul Pantapalangkoor
1Division of General Internal Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles Medical Center, Torrance, CA 90502, United States.
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.
Insights
The rOmpA vaccine dose impacts immune responses against Acinetobacter baumannii. Higher doses enhance Type 2 immunity and epitope spreading, informing vaccine development.
Area of Science:
- Immunology
- Vaccinology
- Microbiology
Background:
- The rOmpA vaccine demonstrates efficacy against extreme-drug-resistant (XDR) Acinetobacter baumannii in murine models.
- The influence of vaccine dosage on the immunological outcomes of the rOmpA vaccine was investigated.
Purpose of the Study:
- To explore the role of vaccine dose in the immunology of the rOmpA vaccine.
- To define the impact of varying rOmpA vaccine doses on antibody titers, cytokine production, and immunodominant epitopes.
Main Methods:
- Mice were immunized with different doses of rOmpA combined with aluminum hydroxide (Al(OH)(3)) adjuvant.
- Analysis included antibody titers, cytokine profiles (IFN-γ, IL-4, IL-17), and epitope mapping of T cell responses.
Main Results:
- Higher rOmpA doses (30 and 100 μg) correlated with increased anti-rOmpA IgG and IgG subtype titers compared to a 3 μg dose.
- The 3 μg dose induced a balanced IFN-γ/IL-4 response, while the 100 μg dose promoted a polarized Type 2 (IL-4 dominant) immune response.
- Epitope mapping identified distinct T cell epitopes, with the 100 μg dose inducing epitope spreading in IL-4-producing cells and restricting IFN-γ-producing cell epitopes.
Conclusions:
- Vaccine dose escalation with rOmpA promotes a Type 2 immune bias, characterized by enhanced IL-4 responses and epitope spreading.
- These findings are crucial for optimizing the rOmpA vaccine against A. baumannii and highlight dose-dependent modulation of immune polarization and epitope selectivity.
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