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A DNA Vaccine against Yellow Fever Virus: Development and Evaluation

Maciel, M and Cruz, FDSP and Cordeiro, MT and da Motta, MA and Cassemiro, KMSDM and Maia, RDCC and de Figueiredo, RCBQ and Galler, R and Freire, MDS and August, JT and Marques, ETA and Dhalia, R (2015) A DNA Vaccine against Yellow Fever Virus: Development and Evaluation. PLoS Neglected Tropical Diseases, 9 (4). ISSN 1935-2727

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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.

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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Maciel, M
Cruz, FDSP
Cordeiro, MT
da Motta, MA
Cassemiro, KMSDM
Maia, RDCC
de Figueiredo, RCBQ
Galler, R
Freire, MDS
August, JT
Marques, ETAmarques@pitt.eduMARQUES0000-0003-3826-9358
Dhalia, R
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorHirayama, KenjiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 13 April 2015
Date Type: Publication
Access Restriction: No restriction; Release the ETD for access worldwide immediately.
Journal or Publication Title: PLoS Neglected Tropical Diseases
Volume: 9
Number: 4
DOI or Unique Handle: 10.1371/journal.pntd.0003693
Institution: University of Pittsburgh
Refereed: Yes
ISSN: 1935-2727
Date Deposited: 25 Jul 2016 14:45
Last Modified: 30 Mar 2021 12:55
URI: http://d-scholarship.pitt.edu/id/eprint/28583

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