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dc.creatorCroyle, Maria A.en
dc.creatorPatel, Amien
dc.creatorTran, Kaylie N.en
dc.creatorGray, Michaelen
dc.creatorZhang, Yien
dc.creatorStrong, James E.en
dc.creatorFeldmann, Heinzen
dc.creatorKobinger, Gary P.en
dc.date.accessioned2013-06-27T16:49:37Zen
dc.date.available2013-06-27T16:49:37Zen
dc.date.issued2008-10-29en
dc.identifier.citationCroyle MA, Patel A, Tran KN, Gray M, Zhang Y, et al. (2008) Nasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Mice. PLoS ONE 3(10): e3548. doi:10.1371/journal.pone.0003548en
dc.identifier.urihttp://hdl.handle.net/2152/20463en
dc.descriptionMaria A. Croyle is with UT Austin, Ami Patel is with the Public Health Agency of Canada and University of Manitoba, Kaylie N. Tran is with the Public Health Agency of Canada, Michael Gray is with the Public Health Agency of Canada, Yi Zhang is with University of Michigan, James E. Strong is with the Public Health Agency of Canada and University of Manitoba, Heinz Feldmann is with the Public Health Agency of Canada and University of Manitoba, Gary P. Kobinger is with the Public Health Agency of Canada and University of Manitoba.en
dc.description.abstractPre-existing immunity to human adenovirus serotype 5 (Ad5) is common in the general population. Bypassing pre-existing immunity could maximize Ad5 vaccine efficacy. Vaccination by the intramuscular (I.M.), nasal (I.N.) or oral (P.O.) route with Ad5 expressing Ebola Zaire glycoprotein (Ad5-ZGP) fully protected naïve mice against lethal challenge with Ebola. In the presence of pre-existing immunity, only mice vaccinated I.N. survived. The frequency of IFN-γ+ CD8+ T cells was reduced by 80% and by 15% in animals vaccinated by the I.M. and P.O. routes respectively. Neutralizing antibodies could not be detected in serum from either treatment group. Pre-existing immunity did not compromise the frequency of IFN-γ+ CD8+ T cells (3.9±1% naïve vs. 3.6±1% pre-existing immunity, PEI) nor anti-Ebola neutralizing antibody (NAB, 40±10 reciprocal dilution, both groups). The number of INF-γ+ CD8+ cells detected in bronchioalveolar lavage fluid (BAL) after I.N. immunization was not compromised by pre-existing immunity to Ad5 (146±14, naïve vs. 120±16 SFC/million MNCs, PEI). However, pre-existing immunity reduced NAB levels in BAL by ~25% in this group. To improve the immune response after oral vaccination, the Ad5-based vaccine was PEGylated. Mice given the modified vaccine did not survive challenge and had reduced levels of IFN-γ+ CD8+ T cells 10 days after administration (0.3±0.3% PEG vs. 1.7±0.5% unmodified). PEGylation did increase NAB levels 2-fold. These results provide some insight about the degree of T and B cell mediated immunity necessary for protection against Ebola virus and suggest that modification of the virus capsid can influence the type of immune response elicited by an Ad5-based vaccine.en
dc.description.sponsorshipNIH, CRTIen
dc.language.isoengen
dc.publisherPublic Library of Scienceen
dc.rightsAttribution 3.0 United Statesen
dc.rightsCC-BYen
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/en
dc.subjectAntibodiesen
dc.subjectCell-mediated immunityen
dc.subjectEbola virusen
dc.subjectEnzyme-linked immunoassaysen
dc.subjectImmune responseen
dc.subjectImmunityen
dc.subjectVaccination and immunizationen
dc.subjectVaccinesen
dc.titleNasal Delivery of an Adenovirus-Based Vaccine Bypasses Pre-Existing Immunity to the Vaccine Carrier and Improves the Immune Response in Miceen
dc.typeArticleen
dc.description.departmentPharmacyen
dc.identifier.doi10.1371/journal.pone.0003548en


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Attribution 3.0 United States
Except where otherwise noted, this item's license is described as Attribution 3.0 United States