Open AccessPreclinical evaluation of a precision medicine approach to DNA vaccination in type 1 diabetes
Author(s) -
Jorge Postigo-Fernandez,
Rebuma Firdessa-Fite,
Rémi J. Creusot
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2110987119
Subject(s) - epitope , dna vaccination , immunology , proinsulin , nod mice , major histocompatibility complex , insulitis , antigen , biology , immunotherapy , mhc class i , vaccination , medicine , autoimmune disease , immune system , antibody , diabetes mellitus , immunization , endocrinology
Significance Antigen-specific immunotherapy may be improved by focusing on epitopes that are disease-relevant and known to be presented on an individual’s human leukocyte antigen (HLA) haplotype, while targeting T cells across multiple antigens and including specific neoepitopes that are not present in protein antigens and/or not produced beyond inflamed sites. Here, we provide proof of principle that such a strategy applied to tolerogenic DNA vaccination is effective in a preclinical model of autoimmune diabetes, paving the way for precision medicine using endogenously encoded epitopes. It takes a minimum number of regular treatments to achieve a level of tolerance and regulation that is needed to limit insulitis and provide sustained protection before treatment may be discontinued or reduced in frequency.