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PLoS Negl Trop Dis. 2015 Apr 13;9(4):e0003693. doi: 10.1371/journal.pntd.0003693. eCollection 2015 Apr.

A DNA vaccine against yellow fever virus: development and evaluation.

Author information

1
Johns Hopkins University, School of Medicine, Department of Pharmacology & Molecular Sciences, Baltimore, Maryland, United States of America.
2
Oswaldo Cruz Foundation (FIOCRUZ), Aggeu Magalhães Research Centre, Department of Virology, Laboratório de Virologia e Terapia Experimental (LAVITE), Universidade Federal de Pernambuco (UFPE), University City, Recife, Pernambuco, Brazil.
3
Oswaldo Cruz Foundation (FIOCRUZ), Aggeu Magalhães Research Centre, Department of Virology, Laboratório de Virologia e Terapia Experimental (LAVITE), Universidade Federal de Pernambuco (UFPE), University City, Recife, Pernambuco, Brazil; Health Secretariat of the State of Pernambuco, Central Public Health Laboratory-LACEN, Boa Vista, Recife, Pernambuco, Brazil.
4
Oswaldo Cruz Foundation (FIOCRUZ), Oswaldo Cruz Institute, Bio-Manguinhos, Laboratório de Tecnologia Virológica (LATEV), Manguinhos, Rio de Janeiro, Brazil.
5
Federal Rural University of Pernambuco, Department of Veterinary Medicine, Dois Irmãos, Recife, Pernambuco, Brazil.
6
Johns Hopkins University, School of Medicine, Department of Pharmacology & Molecular Sciences, Baltimore, Maryland, United States of America; Oswaldo Cruz Foundation (FIOCRUZ), Aggeu Magalhães Research Centre, Department of Virology, Laboratório de Virologia e Terapia Experimental (LAVITE), Universidade Federal de Pernambuco (UFPE), University City, Recife, Pernambuco, Brazil; University of Pittsburgh, Center for Vaccine Research, Pittsburgh, Pennsylvania, United States of America.

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.

PMID:
25875109
PMCID:
PMC4395287
DOI:
10.1371/journal.pntd.0003693
[Indexed for MEDLINE]
Free PMC Article

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