Tags

Type your tag names separated by a space and hit enter

A DNA vaccine against yellow fever virus: development and evaluation.
PLoS Negl Trop Dis. 2015 Apr; 9(4):e0003693.PN

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+Show Affiliations

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.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.Oswaldo Cruz Foundation (FIOCRUZ), Oswaldo Cruz Institute, Bio-Manguinhos, Laboratório de Tecnologia Virológica (LATEV), Manguinhos, Rio de Janeiro, Brazil.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.Federal Rural University of Pernambuco, Department of Veterinary Medicine, Dois Irmãos, Recife, Pernambuco, Brazil.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.Oswaldo Cruz Foundation (FIOCRUZ), Oswaldo Cruz Institute, Bio-Manguinhos, Laboratório de Tecnologia Virológica (LATEV), Manguinhos, Rio de Janeiro, Brazil.Oswaldo Cruz Foundation (FIOCRUZ), Oswaldo Cruz Institute, Bio-Manguinhos, Laboratório de Tecnologia Virológica (LATEV), Manguinhos, Rio de Janeiro, Brazil.Johns Hopkins University, School of Medicine, Department of Pharmacology & Molecular Sciences, Baltimore, Maryland, United States of America.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.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.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25875109

Citation

Maciel, Milton, et al. "A DNA Vaccine Against Yellow Fever Virus: Development and Evaluation." PLoS Neglected Tropical Diseases, vol. 9, no. 4, 2015, pp. e0003693.
Maciel M, Cruz Fda S, Cordeiro MT, et al. A DNA vaccine against yellow fever virus: development and evaluation. PLoS Negl Trop Dis. 2015;9(4):e0003693.
Maciel, M., Cruz, F. d. a. . S., Cordeiro, M. T., da Motta, M. A., Cassemiro, K. M., Maia, R. d. e. . C., de Figueiredo, R. C., Galler, R., Freire, M. d. a. . S., August, J. T., Marques, E. T., & 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
Maciel M, et al. A DNA Vaccine Against Yellow Fever Virus: Development and Evaluation. PLoS Negl Trop Dis. 2015;9(4):e0003693. PubMed PMID: 25875109.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A DNA vaccine against yellow fever virus: development and evaluation. AU - Maciel,Milton,Jr AU - Cruz,Fábia da Silva Pereira, AU - Cordeiro,Marli Tenório, AU - da Motta,Márcia Archer, AU - Cassemiro,Klécia Marília Soares de Melo, AU - Maia,Rita de Cássia Carvalho, AU - de Figueiredo,Regina Célia Bressan Queiroz, AU - Galler,Ricardo, AU - Freire,Marcos da Silva, AU - August,Joseph Thomas, AU - Marques,Ernesto T A, AU - Dhalia,Rafael, Y1 - 2015/04/13/ PY - 2014/08/15/received PY - 2015/03/10/accepted PY - 2015/4/16/entrez PY - 2015/4/16/pubmed PY - 2016/1/26/medline SP - e0003693 EP - e0003693 JF - PLoS neglected tropical diseases JO - PLoS Negl Trop Dis VL - 9 IS - 4 N2 - 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. SN - 1935-2735 UR - https://www.unboundmedicine.com/medline/citation/25875109/A_DNA_vaccine_against_yellow_fever_virus:_development_and_evaluation_ L2 - https://dx.plos.org/10.1371/journal.pntd.0003693 DB - PRIME DP - Unbound Medicine ER -