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dc.contributor.authorAlpert, Michael D.
dc.contributor.authorHarvey, Jackson D.
dc.contributor.authorPiatak, Michael
dc.contributor.authorCarville, Angela
dc.contributor.authorLifson, Jeffrey D.
dc.contributor.authorLi, Wenjun
dc.contributor.authorLauer, William A.
dc.contributor.authorReeves, Roger Keith
dc.contributor.authorMansfield, Keith G.
dc.contributor.authorDesrosiers, Ronald C.
dc.contributor.authorJohnson, R. Paul
dc.contributor.authorEvans, David T.
dc.date.accessioned2013-03-29T15:54:23Z
dc.date.issued2012
dc.identifier.citationAlpert, Michael D., Jackson D. Harvey, W. Anderson Lauer, R. Keith Reeves, Michael Piatak, Angela Carville, Keith G. Mansfield, et al. 2012. ADCC develops over time during persistent infection with live-attenuated SIV and is associated with complete protection against \(SIV_{mac}251\) challenge. PLoS Pathogens 8(8): e1002890.en_US
dc.identifier.issn1553-7366en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10473962
dc.description.abstractLive-attenuated strains of simian immunodeficiency virus (SIV) routinely confer apparent sterilizing immunity against pathogenic SIV challenge in rhesus macaques. Understanding the mechanisms of protection by live-attenuated SIV may provide important insights into the immune responses needed for protection against HIV-1. Here we investigated the development of antibodies that are functional against neutralization-resistant SIV challenge strains, and tested the hypothesis that these antibodies are associated with protection. In the absence of detectable neutralizing antibodies, Env-specific antibody-dependent cell-mediated cytotoxicity (ADCC) emerged by three weeks after inoculation with SIVΔnef, increased progressively over time, and was proportional to SIVΔnef replication. Persistent infection with SIVΔnef elicited significantly higher ADCC titers than immunization with a non-persistent SIV strain that is limited to a single cycle of infection. ADCC titers were higher against viruses matched to the vaccine strain in Env, but were measurable against viruses expressing heterologous Env proteins. In two separate experiments, which took advantage of either the strain-specificity or the time-dependent maturation of immunity to overcome complete protection against \(SIV_{mac}251\) challenge, measures of ADCC activity were higher among the SIVΔnef-inoculated macaques that remained uninfected than among those that became infected. These observations show that features of the antibody response elicited by SIVΔnef are consistent with hallmarks of protection by live-attenuated SIV, and reveal an association between Env-specific antibodies that direct ADCC and apparent sterilizing protection by SIVΔnef.en_US
dc.language.isoen_USen_US
dc.publisherPublic Library of Scienceen_US
dc.relation.isversionofdoi:10.1371/journal.ppat.1002890en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3426556/pdf/en_US
dash.licenseLAA
dc.subjectBiologyen_US
dc.subjectImmunologyen_US
dc.subjectMicrobiologyen_US
dc.subjectModel Organismsen_US
dc.subjectMedicineen_US
dc.subjectInfectious Diseasesen_US
dc.titleADCC Develops Over Time during Persistent Infection with Live-Attenuated SIV and Is Associated with Complete Protection against \(SIV_{mac}251\) Challengeen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalPLoS Pathogensen_US
dash.depositing.authorDesrosiers, Ronald C.
dc.date.available2013-03-29T15:54:23Z
dc.identifier.doi10.1371/journal.ppat.1002890*
dash.authorsorderedfalse
dash.contributor.affiliatedLauer, William A.
dash.contributor.affiliatedJohnson, Robert
dash.contributor.affiliatedEvans, David T.
dash.contributor.affiliatedDesrosiers, Ronald
dash.contributor.affiliatedReeves, Roger


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