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dc.contributor.authorAdnan, Sama
dc.contributor.authorLi, Wenjun
dc.contributor.authorJohnson, R. Paul
dc.date2022-08-11T08:09:46.000
dc.date.accessioned2022-08-23T16:43:07Z
dc.date.available2022-08-23T16:43:07Z
dc.date.issued2016-12-13
dc.date.submitted2017-05-16
dc.identifier.citationPLoS Pathog. 2016 Dec 13;12(12):e1006104. eCollection 2016 Dec. <a href="https://doi.org/10.1371/journal.ppat.1006104">Link to article on publisher's site</a>
dc.identifier.issn1553-7366 (Linking)
dc.identifier.doi10.1371/journal.ppat.1006104
dc.identifier.pmid27959961
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40228
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.abstractDefining the correlates of immune protection conferred by SIVDeltanef, 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 SIVDeltanef 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-SIVDeltanef 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 SIVDeltanef antigenic load. In conclusion, maturation of SIVDeltanef-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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=27959961&dopt=Abstract">Link to Article in PubMed</a>
dc.rightsCopyright © 2016 Adnan et al.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectImmunology of Infectious Disease
dc.subjectMicrobiology
dc.subjectVirus Diseases
dc.titlePersistent Low-Level Replication of SIVDeltanef Drives Maturation of Antibody and CD8 T Cell Responses to Induce Protective Immunity against Vaginal SIV Infection
dc.typeJournal Article
dc.source.journaltitlePLoS pathogens
dc.source.volume12
dc.source.issue12
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4026&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/3021
dc.identifier.contextkey10171428
refterms.dateFOA2022-08-23T16:43:08Z
html.description.abstract<p>Defining the correlates of immune protection conferred by SIVDeltanef, 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 SIVDeltanef 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-SIVDeltanef 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 SIVDeltanef antigenic load. In conclusion, maturation of SIVDeltanef-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.</p>
dc.identifier.submissionpathoapubs/3021
dc.contributor.departmentDepartment of Medicine, Division of Preventive and Behavioral Medicine
dc.source.pagese1006104


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Copyright © 2016 Adnan et al.
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