A DNA Vaccine against Yellow Fever Virus: Development and Evaluation

Attenuated yellow fever (yf) virus 17d/17dd vaccines are the only available protection from yf infection,which remains a significant source of morbidity and mortality in the tropical areas of the world. the attenuated yf virus vaccine,which is used worldwide,generates both long-lasting neutralizing antibodies and strong t-cell responses. however,on rare occasions,this vaccine has toxic side effects that can be fatal. this study presents the design of two non-viral dna-based antigen formulations and the characterization of their expression and immunological properties. the two antigen formulations consist of dna encoding the full-length envelope protein (p/yfe) or the full-length envelope protein fused to the lysosomal-associated membrane protein signal,lamp-1 (pl/yfe),aimed at diverting antigen processing/presentation through the major histocompatibility complex ii precursor compartments. the immune responses triggered by these formulations were evaluated in h2b and h2d backgrounds,corresponding to the c57bl/6 and balb/c mice strains,respectively. both dna constructs were able to induce very strong t-cell responses of similar magnitude against almost all epitopes that are also generated by the yf 17dd vaccine. the pl/yfe formulation performed best overall. in addition to the t-cell response,it was also able to stimulate high titers of anti-yf neutralizing antibodies comparable to the levels elicited by the 17dd vaccine. more importantly,the pl/yfe vaccine conferred 100% protection against the yf virus in intracerebrally challenged mice. these results indicate that pl/yfe dna is an excellent vaccine candidate and should be considered for further developmental studies. © 2015 maciel et al.