• Home
  • Search Results
  • Vaccines targeting self-antigens: mechanisms and efficacy-determining parameters.

Vaccines targeting self-antigens: mechanisms and efficacy-determining parameters.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology (2015-04-15)
Falk Saupe, Elisabeth J M Huijbers, Tobias Hein, Julia Femel, Jessica Cedervall, Anna-Karin Olsson, Lars Hellman
ABSTRACT

We recently showed that it is possible to compromise tumor vessel function and, as a consequence, suppress growth of aggressive preclinical tumors by immunizing against the tumor vascular markers extra domain-A (ED-A) or -B (ED-B) of fibronectin, using a fusion protein consisting of the ED-A or ED-B peptide fused to bacterial thioredoxin. To address the mechanism behind fusion protein-induced immunization and the specific contribution of the different vaccine constituents to elicit an anti-self-antibody response, we immunized mice with modified or unmodified self-antigens, combined with different adjuvant components, and analyzed antibody responses by ELISA in sera. Several essential requirements to circumvent tolerance were identified: (1) a potent pattern recognition receptor agonist like an oligonucleotide containing unmethylated cytosine and guanine dinucleotides (CpG); (2) a depot adjuvant to keep the CpG at the site of injection; and (3) the presence of foreign sequences in the vaccine protein. Lack of either of these factors abolished the anti-self-response (P = 0.008). In mice genetically deficient for type I IFN signaling, there was a 60% reduction in the anti-self-response compared with wild-type (P = 0.011), demonstrating a key role of this pathway in CpG-induced circumvention of self-tolerance. Identification of these mechanistic requirements to generate a potent anti-self-immune response should significantly aid the design of efficient, specific, and safe therapeutic cancer vaccines.

MATERIALS
Product Number
Brand
Product Description

SAFC
BIS-TRIS
Sigma-Aldrich
Bicinchoninic acid disodium salt hydrate, ≥98% (HPLC)
Sigma-Aldrich
Imidazole, ACS reagent, ≥99% (titration)
Sigma-Aldrich
Imidazole, ≥99% (titration), crystalline
Sigma-Aldrich
Imidazole, for molecular biology, ≥99% (titration)
Sigma-Aldrich
BIS-TRIS, ≥98.0% (titration)
Sigma-Aldrich
BIS-TRIS, BioPerformance Certified, suitable for cell culture, suitable for insect cell culture, ≥98.0%
Sigma-Aldrich
BIS-TRIS, BioXtra, ≥98.0% (titration)
Sigma-Aldrich
Imidazole, puriss. p.a., ≥99.5% (GC)
Sigma-Aldrich
Imidazole, ReagentPlus®, 99%
Sigma-Aldrich
BIS-TRIS, BioUltra, ≥99.0% (NT)
Sigma-Aldrich
Imidazole, BioUltra, for molecular biology, ≥99.5% (GC)
Sigma-Aldrich
Imidazole, BioUltra, ≥99.5% (GC)
Sigma-Aldrich
Imidazole, for molecular biology, ≥99% (titration), free-flowing, Redi-Dri
Sigma-Aldrich
Imidazole, ReagentPlus®, 99%, Redi-Dri, free-flowing
SAFC
BIS-TRIS
Sigma-Aldrich
Imidazole, anhydrous, free-flowing, Redi-Dri, ACS reagent, ≥99%
Sigma-Aldrich
Imidazole buffer Solution, BioUltra, 1 M in H2O