Vaccination with gag, vif, and nef Gene Fragments Affords Partial Control of Viral Replication after Mucosal Challenge with SIVmac239

dc.creatorMartins, Mauricio A.
dc.creatorWilson, Nancy A.
dc.creatorPlaskowski, Shari M.
dc.creatorWeisgrau, Kim L.
dc.creatorFurlott, Jessica R.
dc.creatorBonaldo, Myrna C.
dc.creatorSantana, Marlon G. Veloso de
dc.creatorRudersdorf, Richard A.
dc.creatorRakasz, Eva G.
dc.creatorKeating, Karen D.
dc.creatorChiuchiolo, Maria J.
dc.creatorPlatak Jr, Michael
dc.creatorAllison, David B.
dc.creatorParks, Christopher L.
dc.creatorGaller, Ricardo
dc.creatorLifson, Jeffrey D.
dc.creatorWatkins, David I.
dc.date2015-05-04T17:07:28Z
dc.date2015-05-04T17:07:28Z
dc.date2014
dc.date.accessioned2023-09-26T23:53:06Z
dc.date.available2023-09-26T23:53:06Z
dc.identifierMARTINS, Mauricio A. et al. Vaccination with gag, vif, and nef Gene Fragments Affords Partial Control of Viral Replication after Mucosal Challenge with SIVmac239. Journal of Virology, v.88, n.13, p. 7493-7516, 2014.
dc.identifier1098-5514
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/10198
dc.identifier10.1128/JVI.00601-14
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8895249
dc.descriptionBroadly targeted cellular immune responses are thought to be important for controlling replication of human and simian immunodeficiency viruses (HIV and SIV). However, eliciting such responses by vaccination is complicated by immunodominance, the preferential targeting of only a few of the many possible epitopes of a given antigen. This phenomenon may be due to the coexpression of dominant and subdominant epitopes by the same antigen-presenting cell and may be overcome by distributing these sequences among several different vaccine constructs. Accordingly, we tested whether vaccinating rhesus macaques with “minigenes” encoding fragments of Gag, Vif, and Nef resulted in broadened cellular responses capable of controlling SIV replication.Wedelivered these minigenes through combinations of recombinant Mycobacterium bovis BCG (rBCG), electroporated recombinant DNA (rDNA) along with an interleukin-12 (IL-12)-expressing plasmid (EP rDNA plus pIL-12), yellow fever vaccine virus 17D (rYF17D), and recombinant adenovirus serotype 5 (rAd5). Although priming with EP rDNA plus pIL-12 increased the breadth of vaccine-induced T-cell responses, this effect was likely due to the improved antigen delivery afforded by electroporation rather than modulation of immunodominance. Indeed, Mamu-A*01 vaccinees mounted CD8 T cells directed against only one subdominant epitope, regardless of the vaccination regimen. After challenge with SIVmac239, vaccine efficacy was limited to a modest reduction in set point in some of the groups and did not correlate with standard T-cell measurements. These findings suggest that broad T-cell responses elicited by conventional vectors may not be sufficient to substantially contain AIDS virus replication.
dc.formatapplication/pdf
dc.languageeng
dc.publisherAmerican Society for Microbiology
dc.rightsopen access
dc.subjectHIV
dc.subjectHuman and simian immunodeficiency viruses (HIV and SIV)
dc.subjectHIV
dc.subjectVaccination regimens
dc.subjectT-cell responses
dc.subjectHIV
dc.subjectCiências Biológicas
dc.titleVaccination with gag, vif, and nef Gene Fragments Affords Partial Control of Viral Replication after Mucosal Challenge with SIVmac239
dc.typeArticle


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