Heterologous peptide display on chromatin nanofibres: a new stategy for peptide vaccines

Chromatin organization starts from a “beads-on-a string” 10 nm fibre, a basic nucleosomal structure consisting of DNA and core histones. Given its regular nucleosome array on DNA backbone where N-terminal tails of each histone are exposed on the surface of chromatin fibre, we hypothesized that chromatin can be utilized as a heterologous peptide carrier to elicit a peptide-specific immune response. The plasmid DNA containing the Widom's clone 601 sequence and the recombinant chimeric histones containing the peptide derived from ras oncogene (G12V) were used to assemble the chromatin fibre in vitro. The immunogenicity of the assembled chromatin was tested in mice as a single vaccine component or formulated with adjuvants. The results showed that G12V tagged-chromatin co-administered with the adjuvants induced a higher antibody response against the G12V peptide than vaccination with the adjuvant alone, while chimeric histones failed to generate a significant antibody response. Interestingly, antigen-stimulated splenocytes from mice vaccinated with the G12V tagged-chromatin did not generate significant cytokine responses, suggesting that a repetitive peptide display on the chromatin induces an antibody response while suppressing cytokine secretion in T cells. These studies suggest that chromatin can be utilized as an effective carrier of antigenic peptides for inducing specific antibody responses.