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| Status |
Public on Feb 20, 2021 |
| Title |
Pore-forming toxin alpha-hemolysin efficiently improve the immunogenicity and protective efficacy of protein antigens by increasing antigen uptake and targeting ADAM10 |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Highly immunogenic exotoxins were proved to be efficient in improving the immunogenicity of polysaccharides, traditionally known as carrier proteins. However, the efficacy of exotoxins on protein antigens remains to be excluded. In the current study, the candidate antigen PA0833 from Pseudomonas aeruginosa was fused to the α-hemolysin mutant HlaH35A from Staphylococcus aureus. After immunization with the fusion protein, increased titers of PA0833-specific antibodies and higher protective efficacy were observed, companied with decreased bacterial burden and pro-inflammatory cytokines secretion when compared with PA0833 immunization alone. Then, by using fluorescently labeled antigens to track antigen uptake and delivery, we found that fusion to HlaH35A significantly improved antigen uptake in injected muscles and antigen delivery to draining lymph nodes. Both in vivo and in vitro studies demonstrated that increased antigen uptake by fusion to HlaH35A were mainly mediated by monocytes and macrophages in a macropinocytosis dependent manner, probably due to targeting ADAM10, the host receptor of Hla. Further, transcriptome analysis was performed and the result showed that several immune signaling pathways were activated by HPF, which also shed light on the mechanism of improved immunogenicity. Finally, improvement of immunogenicity by fusion to HlaH35A was also confirmed in two other anigens, GlnH from Klebsiella pneumoniae and the model antigen OVA, which indicated that HlaH35A could serve as a universal carrier protein to improve the immunogenicity of protein antigens.
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| Overall design |
mRNA profiles of Raw264.7 cell at 6-hours post treated with His buffer, PA0833, Hla-PA0833(HPF)
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| Contributor(s) |
Zou J, Zhang J, Zou Q |
| Citation(s) |
34288976 |
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| Submission date |
Feb 19, 2021 |
| Last update date |
Aug 06, 2021 |
| Contact name |
Jintao Zou |
| E-mail(s) |
jintaozou1993@outlook.com
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| Organization name |
Army Medical University
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| Street address |
Gaotanyanstreet
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| City |
Chongqing |
| State/province |
China |
| ZIP/Postal code |
400038 |
| Country |
China |
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| Platforms (1) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA702922 |
| SRA |
SRP307099 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE167077_RAW.tar |
1.6 Mb |
(http)(custom) |
TAR (of TXT) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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