Codon-Optimized P1A-Encoding DNA Vaccine: Toward a Therapeutic Vaccination against P815 Mastocytoma

Abstract

DNA vaccine can be modified to increase protein production and modulate immune response. To enhance the efficiency of a P815 mastocytoma DNA vaccine, the P1A gene sequence was optimized by substituting specific codons with synonymous ones while modulating the number of CpG motifs. The P815A murine antigen production was increased with codon-optimized plasmids. The number of CpG motifs within the P1A gene sequence modulated the immunogenicity by inducing a local increase in the cytokines involved in innate immunity. After prophylactic immunization with the optimized vaccines, tumor growth was significantly delayed and mice survival was improved. Consistently, a more pronounced intratumoral recruitment of CD8+ T cells and a memory response were observed. Therapeutic vaccination was able to delay tumor growth when the codon-optimized DNA vaccine containing the highest number of CpG motifs was used. Our data demonstrate the therapeutic potential of optimized P1A vaccine against P815 mastocytoma, and they show the dual role played by codon optimization on both protein production and innate immune activation. Keywords: codon optimization, DNA vaccine, P815, P1A, prophylactic, therapeutic vaccine, CpG, innate immunity, cancer vaccine, tumor vaccine