Comparison of PLA Microparticles and Alum as Adjuvants for H5N1 Influenza Split Vaccine: Adjuvanticity Evaluation and Preliminary Action Mode Analysis
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To compare the adjuvanticity of polymeric particles (new-generation adjuvant) and alum (the traditional and FDA-approved adjuvant) for H5N1 influenza split vaccine, and to investigate respective action mode.
Vaccine formulations were prepared by incubating lyophilized poly(lactic acid) (PLA) microparticles or alum within antigen solution. Antigen-specific immune responses in mice were evaluated using ELISA, ELISpot, and flow cytometry assay. Adjuvants’ action modes were investigated by determining antigen persistence at injection sites, local inflammation response, antigen transport into draining lymph node, and activation of DCs in secondary lymphoid organs (SLOs).
Alum promoted antigen-specific humoral immune response. PLA microparticles augmented both humoral immune response and cell-mediated-immunity which might enhance cross-protection of influenza vaccine. With regard to action mode, alum adjuvant functions by improving antigen persistence at injection sites, inducing severe local inflammation, slightly improving antigen transport into draining lymph nodes, and improving the expression of MHC II on DCs in SLOs. PLA microparticles function by slightly improving antigen transport into draining lymph nodes, and promoting the expression of both MHC molecules and co-stimulatory molecules on DCs in SLOs.
Considering the adjuvanticity and side effects (local inflammation) of both adjuvants, we conclude that PLA microparticles are promising alternative adjuvant for H5N1 influenza split vaccine.
Key wordsadjuvanticity alum influenza vaccine microparticles mode of action
Antigen presenting cell
Bovine serum albumin
Enzyme-linked immunosorbant assay
Major histocompatibility complex
Oil in water
Standard errors of mean
Secondary lymphoid organs
Acknowledgments and Disclosures
The authors gratefully thank Dr Wei Wei for assistance with CLSM characterization of PLA microparticles-adjuvanted vaccine formulation. This work was financially supported by the 973 Program (Grant No. 2013CB531500), the Knowledge Innovation Program of the Chinese Academy of Sciences (Grant No. KSCX2-EW-R-19), and the 863 Program (Grant No. 2012AA02A406).
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