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dc.contributor.authorAdnan, Samaen_US
dc.contributor.authorReeves, R. Keithen_US
dc.contributor.authorGillis, Jacquelineen_US
dc.contributor.authorWong, Fay E.en_US
dc.contributor.authorYu, Yien_US
dc.contributor.authorCamp, Jeremy V.en_US
dc.contributor.authorLi, Qingshengen_US
dc.contributor.authorConnole, Michelleen_US
dc.contributor.authorLi, Yuanen_US
dc.contributor.authorPiatak, Michaelen_US
dc.contributor.authorLifson, Jeffrey D.en_US
dc.contributor.authorLi, Wenjunen_US
dc.contributor.authorKeele, Brandon F.en_US
dc.contributor.authorKozlowski, Pamela A.en_US
dc.contributor.authorDesrosiers, Ronald C.en_US
dc.contributor.authorHaase, Ashley T.en_US
dc.contributor.authorJohnson, R. Paulen_US
dc.date.accessioned2017-02-18T01:59:40Z
dc.date.issued2016en_US
dc.identifier.citationAdnan, S., R. K. Reeves, J. Gillis, F. E. Wong, Y. Yu, J. V. Camp, Q. Li, et al. 2016. “Persistent Low-Level Replication of SIVΔnef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infection.” PLoS Pathogens 12 (12): e1006104. doi:10.1371/journal.ppat.1006104. http://dx.doi.org/10.1371/journal.ppat.1006104.en
dc.identifier.issn1553-7366en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:30371148
dc.description.abstractDefining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals. Multiple parameters of CD8 T cell function temporally correlated with maturation of protection, including polyfunctionality, phenotypic differentiation, and redistribution to gut and lymphoid tissues. Importantly, we also demonstrate the induction of a tissue-resident memory population of SIV-specific CD8 T cells in the vaginal mucosa, which was dependent on ongoing low-level antigenic stimulation. Moreover, we show that vaginal and serum antibody titers inversely correlated with post-challenge peak viral load, and we correlate the accumulation and affinity maturation of the antibody response to the duration of the vaccination period as well as to the SIVΔnef antigenic load. In conclusion, maturation of SIVΔnef-induced CD8 T cell and antibody responses, both propelled by viral persistence in the gut mucosa and secondary lymphoid tissues, results in protective immune responses that are able to interrupt viral transmission at mucosal portals of entry as well as potential sites of viral dissemination.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.ppat.1006104en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5189958/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectCell Biologyen
dc.subjectCellular Typesen
dc.subjectAnimal Cellsen
dc.subjectBlood Cellsen
dc.subjectWhite Blood Cellsen
dc.subjectT Cellsen
dc.subjectImmune Cellsen
dc.subjectImmunologyen
dc.subjectMedicine and Health Sciencesen
dc.subjectBiology and life sciencesen
dc.subjectCell biologyen
dc.subjectCellular typesen
dc.subjectAnimal cellsen
dc.subjectBlood cellsen
dc.subjectWhite blood cellsen
dc.subjectT cellsen
dc.subjectCytotoxic T cellsen
dc.subjectImmune cellsen
dc.subjectMedicine and health sciencesen
dc.subjectVaccination and Immunizationen
dc.subjectPublic and Occupational Healthen
dc.subjectPreventive Medicineen
dc.subjectPhysiologyen
dc.subjectImmune Physiologyen
dc.subjectAntibodiesen
dc.subjectImmune System Proteinsen
dc.subjectBiochemistryen
dc.subjectProteinsen
dc.subjectInfectious Diseasesen
dc.subjectViral Diseasesen
dc.subjectViremiaen
dc.subjectMicrobiologyen
dc.subjectMedical Microbiologyen
dc.subjectMicrobial Pathogensen
dc.subjectViral Pathogensen
dc.subjectImmunodeficiency Virusesen
dc.subjectSIVen
dc.subjectPathology and Laboratory Medicineen
dc.subjectPathogensen
dc.subjectOrganismsen
dc.subjectVirusesen
dc.subjectRNA virusesen
dc.subjectRetrovirusesen
dc.subjectLentivirusen
dc.subjectImmune Responseen
dc.subjectAntibody Responseen
dc.subjectImmunologic Techniquesen
dc.subjectImmunoassaysen
dc.subjectEnzyme-Linked Immunoassaysen
dc.titlePersistent Low-Level Replication of SIVΔnef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infectionen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS Pathogensen
dash.depositing.authorYu, Yien_US
dc.date.available2017-02-18T01:59:40Z
dc.identifier.doi10.1371/journal.ppat.1006104*
dash.authorsorderedfalse
dash.contributor.affiliatedYu, Yi


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