title: A DNA vaccine against yellow fever virus: development and evaluation.
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.
authors: Johns Hopkins University, School of Medicine, Department of Pharmacology & Molecular Sciences, Baltimore, Maryland, United States of America.
authors: Milton
authors: M
authors: Maciel
authors: 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.
authors: Fábia da Silva Pereira
authors: Fda S
authors: Cruz
authors: 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.
authors: Marli Tenório
authors: MT
authors: Cordeiro
authors: Oswaldo Cruz Foundation (FIOCRUZ), Oswaldo Cruz Institute, Bio-Manguinhos, Laboratório de Tecnologia Virológica (LATEV), Manguinhos, Rio de Janeiro, Brazil.
authors: Márcia Archer
authors: MA
authors: da Motta
authors: 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.
authors: Klécia Marília Soares de Melo
authors: KM
authors: Cassemiro
authors: Federal Rural University of Pernambuco, Department of Veterinary Medicine, Dois Irmãos, Recife, Pernambuco, Brazil.
authors: Rita de Cássia Carvalho
authors: Rde C
authors: Maia
authors: 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.
authors: Regina Célia Bressan Queiroz
authors: RC
authors: de Figueiredo
authors: Oswaldo Cruz Foundation (FIOCRUZ), Oswaldo Cruz Institute, Bio-Manguinhos, Laboratório de Tecnologia Virológica (LATEV), Manguinhos, Rio de Janeiro, Brazil.
authors: Ricardo
authors: R
authors: Galler
authors: Oswaldo Cruz Foundation (FIOCRUZ), Oswaldo Cruz Institute, Bio-Manguinhos, Laboratório de Tecnologia Virológica (LATEV), Manguinhos, Rio de Janeiro, Brazil.
authors: Marcos da Silva
authors: Mda S
authors: Freire
authors: Johns Hopkins University, School of Medicine, Department of Pharmacology & Molecular Sciences, Baltimore, Maryland, United States of America.
authors: Joseph Thomas
authors: JT
authors: August
authors: 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.
authors: Ernesto T A
authors: ET
authors: Marques
authors: 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.
authors: Rafael
authors: R
authors: Dhalia
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology; D019444:Vaccines, DNA / Q000276:immunology; D015004:Yellow Fever / Q000517:prevention & control* / Q000821:virology; D022341:Yellow Fever Vaccine / Q000276:immunology*; D015005:Yellow fever virus / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D014613:Vaccines, Attenuated; D019444:Vaccines, DNA; D022341:Yellow Fever Vaccine