The S. aureus 4-oxalocrotonate tautomerase SAR1376 enhances immune responses when fused to several antigens

Scientific Reports
Pauline M van DiemenDavid H Wyllie

Abstract

A persistent goal of vaccine development is the enhancement of the immunogenicity of antigens while maintaining safety. One strategy involves alteration of the presentation of the antigen by combining antigens with a multimeric scaffold. Multi-antigen vaccines are under development, and there are presently far more candidate antigens than antigen scaffolding strategies. This is potentially problematic, since prior immunity to a scaffold may inhibit immune responses to the antigen-scaffold combination. In this study, a series of domains from S. aureus which have been shown to crystallise into multimeric structures have been examined for their scaffolding potential. Of these domains, SAR1376, a 62 amino acid member of the 4-oxalocrotonate tautomerase (4-OT) family, was pro-immunogenic in mice when fused to a range of pathogen antigens from both S. aureus and P. falciparum, and delivered by either DNA vaccination, viral vector vaccines or as protein-in-adjuvant formulations. The adjuvant effect did not depend on enzymatic activity, but was abrogated by mutations disrupting the hexameric structure of the protein. We therefore propose that SAR1376, and perhaps other members of the 4-OT protein family, represent very small domains wh...Continue Reading

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Citations

Aug 3, 2021·Frontiers in Immunology·Hans de GraafSumi Biswas

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Methods Mentioned

BETA
ELISA
Assay

Software Mentioned

R
GraphPad Prism
PhyML
Archeopterix
CEAlign
Pymol
Cobalt engine
delta
BLASTp
BLAST

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