Vaccines targeting self-antigens: mechanisms and efficacy-determining parameters
2015
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 proteinconsisting 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 receptoragonist 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...
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