@article{f3432a2c8b1c47afb688c61361d9103d,
title = "Induction of broad cytotoxic T cells by protective DNA vaccination against Marburg and Ebola",
abstract = "Marburg and Ebola hemorrhagic fevers have been described as the most virulent viral diseases known to man due to associative lethality rates of up to 90%. Death can occur within days to weeks of exposure and there is currently no licensed vaccine or therapeutic. Recent evidence suggests an important role for antiviral T cells in conferring protection, but little detailed analysis of this response as driven by a protective vaccine has been reported. We developed a synthetic polyvalent-filovirus DNA vaccine against Marburg marburgvirus (MARV), Zaire ebolavirus (ZEBOV), and Sudan ebolavirus (SUDV). Preclinical efficacy studies were performed in guinea pigs and mice using rodent-adapted viruses, whereas murine T-cell responses were extensively analyzed using a novel modified assay described herein. Vaccination was highly potent, elicited robust neutralizing antibodies, and completely protected against MARV and ZEBOV challenge. Comprehensive T-cell analysis revealed cytotoxic T lymphocytes (CTLs) of great magnitude, epitopic breadth, and T h 1-type marker expression. This model provides an important preclinical tool for studying protective immune correlates that could be applied to existing platforms. Data herein support further evaluation of this enhanced gene-based approach in nonhuman primate studies for in depth analyses of T-cell epitopes in understanding protective efficacy.",
author = "Shedlock, {Devon J.} and Jenna Aviles and Talbott, {Kendra T.} and Gary Wong and Wu, {Stephan J.} and Villarreal, {Daniel O.} and Myles, {Devin J.F.} and Croyle, {Maria A.} and Jian Yan and Kobinger, {Gary P.} and Weiner, {David B.}",
note = "Funding Information: We acknowledge Karuppiah Muthumani, and members of the Weiner and Kobinger laboratories for significant discussion, contributions, and/or critical reading of this manuscript. In addition, Charles H Pletcher, Andrew D Bantly, Richard D Schretzenmair, William J DeMuth III, Gisela N BrakeSill{\'a}, and the University of Pennsylvania Path BioResource Flow Cytometry & Cell Sorting Facility staff are acknowledged for their generous technical assistance. This work was supported by NIH, NIAID, and/or DAIDS grants: HIV Vaccine Research and Design (HIVRAD) (P01-AI071739) and “Development of a Universal Influenza Seasonal Vaccine” (R01-AI092843) to D.B.W., and by funding to D.B.W. and D.J.S. (T32-AI070099). Also, the work was supported in part by {"}Evaluation of Protective Immunity after Mucosal Vaccination Against Ebola Virus{"} (V01-AI078045). In addition, funding from Inovio Pharmaceuticals was received as part of Sponsored Research Agreements entitled “Study and Development of Consensus Immunogens in the area of Viral Vaccines” and {"}Consensus Immunogens.{"} For disclosure purposes, D.B.W. notes that he and his laboratory have several commercial relationships with companies in the area of vaccines. These include him receiving consulting fees or stock ownership for Advisory/Review Board service, speaking support, or research support from commercial entities including Inovio Pharmaceuticals, Bristol-Myers Squibb, VGXI, Pfizer, Virxsys Co., Johnson & Johnson, Merck & Co., Sanofi Pasteur, Althea, Novo Nordisk, Statens Serum Institut, Aldevron, Novartis, Incyte, and possibly others. The other authors declare no conflict of interest.",
year = "2013",
month = jul,
doi = "10.1038/mt.2013.61",
language = "English (US)",
volume = "21",
pages = "1432--1444",
journal = "Molecular Therapy",
issn = "1525-0016",
publisher = "Nature Publishing Group",
number = "7",
}