{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T06:59:37Z","timestamp":1790492377682,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1008954","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2020,11,5]],"date-time":"2020-11-05T00:00:00Z","timestamp":1604534400000}}],"reference-count":49,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T00:00:00Z","timestamp":1603670400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI133706"],"award-info":[{"award-number":["R01AI133706"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P01AI131276"],"award-info":[{"award-number":["P01AI131276"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P51OD011132"],"award-info":[{"award-number":["P51OD011132"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P30CA138292"],"award-info":[{"award-number":["P30CA138292"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["P30AI050409"],"award-info":[{"award-number":["P30AI050409"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Globally, 1.8 million children are living with HIV-1. While antiretroviral therapy (ART) has improved disease outcomes, it does not eliminate the latent HIV-1 reservoir. Interventions to delay or prevent viral rebound in the absence of ART would be highly beneficial for HIV-1-infected children who now must remain on daily ART throughout their lifespan. Here, we evaluated therapeutic Ad48-SIV prime, MVA-SIV boost immunization in combination with the TLR-7 agonist GS-986 in rhesus macaque (RM) infants orally infected with SIV<jats:sub>mac251<\/jats:sub>at 4 weeks of age and treated with a triple ART regimen beginning 4 weeks after infection. We hypothesized immunization would enhance SIV-specific T cell responses during ART-mediated suppression of viremia. Compared to controls, vaccinated infants had greater magnitude SIV-specific T cell responses (mean of 3475 vs 69 IFN-<jats:italic>\u03b3<\/jats:italic>spot forming cells (SFC) per 10<jats:sup>6<\/jats:sup>PBMCs, respectively, P = 0.01) with enhanced breadth of epitope recognition and increased CD8<jats:sup>+<\/jats:sup>and CD4<jats:sup>+<\/jats:sup>T cell polyfunctionality (P = 0.004 and P = 0.005, respectively). Additionally, SIV-specific gp120 antibodies against challenge and vaccine virus strains were significantly elevated following MVA boost (P = 0.02 and P &lt; 0.001, respectively). GS-986 led to expected immune stimulation demonstrated by activation of monocytes and T cells 24 hours post-dose. Despite the vaccine-induced immune responses, levels of SIV DNA in peripheral and lymph node CD4<jats:sup>+<\/jats:sup>T cells were not significantly different from controls and a similar time to viral rebound and viral load set point were observed following ART interruption in both groups. We demonstrate infant RMs mount a robust immunological response to this immunization, but vaccination alone was not sufficient to impact viral reservoir size or modulate rebound dynamics following ART release. Our findings hold promise for therapeutic vaccination as a part of a combination cure approach in children and highlight the importance of a pediatric model to evaluate HIV-1 cure interventions in this unique setting of immune development.<\/jats:p>","DOI":"10.1371\/journal.ppat.1008954","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T18:47:18Z","timestamp":1603738038000},"page":"e1008954","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":31,"title":["Therapeutic vaccination of SIV-infected, ART-treated infant rhesus macaques using Ad48\/MVA in combination with TLR-7 stimulation"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3339-0175","authenticated-orcid":true,"given":"Katherine M.","family":"Bricker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6034-1443","authenticated-orcid":true,"given":"Veronica","family":"Obregon-Perko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferzan","family":"Uddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brianna","family":"Williams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5902-0028","authenticated-orcid":true,"given":"Emilie A.","family":"Uffman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Garrido","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0960-1019","authenticated-orcid":true,"given":"Genevieve G.","family":"Fouda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romas","family":"Geleziunas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3949-9649","authenticated-orcid":true,"given":"Merlin","family":"Robb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelson","family":"Michael","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan H.","family":"Barouch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7479-9546","authenticated-orcid":true,"given":"Ann","family":"Chahroudi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,10,26]]},"reference":[{"key":"ppat.1008954.ref001","unstructured":"UNAIDS. 2020 Fact Sheet [10\/06\/2020]. Available from: https:\/\/www.unaids.org\/en\/resources\/fact-sheet."},{"issue":"8","key":"ppat.1008954.ref002","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1056\/NEJMra1505256","article-title":"Challenges in the Elimination of Pediatric HIV-1 Infection","volume":"374","author":"K Luzuriaga","year":"2016","journal-title":"N Engl J Med"},{"issue":"24","key":"ppat.1008954.ref003","doi-asserted-by":"crossref","first-page":"13193","DOI":"10.1073\/pnas.94.24.13193","article-title":"Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy","volume":"94","author":"TW Chun","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5341","key":"ppat.1008954.ref004","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1126\/science.278.5341.1295","article-title":"Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy","volume":"278","author":"D Finzi","year":"1997","journal-title":"Science"},{"issue":"3","key":"ppat.1008954.ref005","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.cell.2013.09.020","article-title":"Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure","volume":"155","author":"YC Ho","year":"2013","journal-title":"Cell"},{"issue":"9210","key":"ppat.1008954.ref006","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1016\/S0140-6736(00)02061-4","article-title":"Time from HIV-1 seroconversion to AIDS and death before widespread use of highly-active antiretroviral therapy: a collaborative re-analysis. 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cytomegalovirus-specific, CD8(+) T cell responses in young HIV-1-infected infants","volume":"167","author":"ZA Scott","year":"2001","journal-title":"J Immunol"},{"issue":"439","key":"ppat.1008954.ref030","article-title":"TLR7 agonists induce transient viremia and reduce the viral reservoir in SIV-infected rhesus macaques on antiretroviral therapy","volume":"10","author":"SY Lim","year":"2018","journal-title":"Sci Transl Med."},{"issue":"11","key":"ppat.1008954.ref031","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.127717","article-title":"TLR7 agonist administration to SIV-infected macaques receiving early initiated cART does not induce plasma viremia","volume":"4","author":"GQ Del Prete","year":"2019","journal-title":"JCI Insight"},{"issue":"7731","key":"ppat.1008954.ref032","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/s41586-018-0600-6","article-title":"Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys","volume":"563","author":"EN Borducchi","year":"2018","journal-title":"Nature"},{"issue":"11","key":"ppat.1008954.ref033","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.01163-19","article-title":"PD-1 Blockade and TLR7 Activation Lack Therapeutic Benefit in Chronic Simian Immunodeficiency Virus-Infected Macaques on Antiretroviral Therapy","volume":"63","author":"E Bekerman","year":"2019","journal-title":"Antimicrob Agents Chemother"},{"key":"ppat.1008954.ref034","first-page":"23","volume-title":"HIV-1 Latency","author":"JD Siliciano","year":"2018"},{"issue":"1","key":"ppat.1008954.ref035","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.chom.2019.06.005","article-title":"The Landscape of Persistent Viral Genomes in ART-Treated SIV, SHIV, and HIV-2 Infections","volume":"26","author":"AM Bender","year":"2019","journal-title":"Cell Host Microbe"},{"issue":"7742","key":"ppat.1008954.ref036","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1038\/s41586-019-0898-8","article-title":"A 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