Oligomerization of IC43 resulted in improved immunogenicity and protective efficacy against Pseudomonas aeruginosa lung infection
2020
Jing, Haiming | Zhang, Xiaoli | Zou, Jintao | Yuan, Yue | Chen, Zhifu | Liu, Dong | Wu, Weiru | Yang, Feng | Lu, Dongshui | Zou, Quanming | Zhang, Jinyong
IC43, a truncate form of outer membrane proteins OprF₁₉₀–₃₄₂ and OprI₂₁–₈₃ from Pseudomonas aeruginosa, is a promising candidate antigen and exists as monomer in solution. In this study, we generated the heptamer of IC43 by carrier protein aided oligomerization, which was confirmed by gel-filtration and chemical cross-linking analysis. The carrier protein naturally exists as a homo-heptamer, and IC43 was displayed on the surface of the carrier protein in the fusion protein. Immunization with this fusion protein resulted in increased level of antigen specific IgG antibodies and higher survival rate after infection. The improved efficacy was correlated with lower bacteria burden, inflammation and tissue damage in the lungs of immunized mice. Further studies revealed that immunization with this fusion protein resulted in increased levels of IL-4 and antigen specific IgG1, suggesting a stronger Th2 immune response was induced. The improved immunogenicity may be attributed to the exposure of more epitopes on the antigen, which was confirmed by results from immune-dominant peptide mapping and passive immunization. These results demonstrated a possible strategy to improve the immunogenicity of an antigen by carrier protein aided oligomerization.
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