A DNA Vaccine against Yellow Fever Virus: Development and Evaluation

Milton Maciel, Fábia da Silva Pereira Cruz, Marli Tenório Cordeiro, Márcia Archer da Motta, Klécia Marília Soares de Melo Cassemiro, Rita de Cássia Carvalho Maia, Regina Célia Bressan Queiroz de Figueiredo, Ricardo Galler, Marcos da Silva Freire, Joseph Thomas August, Ernesto T.A. Marques, Rafael Dhalia

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbere0003693
JournalPLoS neglected tropical diseases
Volume9
Issue number4
DOIs
StatePublished - Apr 13 2015

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Infectious Diseases

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  • Cite this

    Maciel, M., Cruz, F. D. S. P., Cordeiro, M. T., da Motta, M. A., Cassemiro, K. M. S. D. M., Maia, R. D. C. C., de Figueiredo, R. C. B. Q., Galler, R., Freire, M. D. S., August, J. T., Marques, E. T. A., & Dhalia, R. (2015). A DNA Vaccine against Yellow Fever Virus: Development and Evaluation. PLoS neglected tropical diseases, 9(4), [e0003693]. https://doi.org/10.1371/journal.pntd.0003693