{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T11:56:12Z","timestamp":1793102172335,"version":"4.5.0"},"reference-count":53,"publisher":"SAGE Publications","issue":"12","license":[{"start":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T00:00:00Z","timestamp":1755648000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["AIDS Research and Human Retroviruses"],"published-print":{"date-parts":[[2025,12,1]]},"abstract":"<jats:p>\n                    Adeno-associated virus (AAV)-vectored delivery of HIV-1 broadly neutralizing antibodies (bNAbs) holds promise for achieving durable HIV-1 immunity in a practical and scalable way, yet AAV-encoded bNAbs often elicit antidrug antibody (ADA) responses that limit transgene expression. Engagement of T cell-expressed CD28 with its ligands CD80\/CD86 on professional antigen-presenting cells is crucial for initiating adaptive immunity. Because the immunoglobulin-fusion protein CTLA4Ig can outcompete CD28 for binding to CD80\/CD86, CTLA4Ig can inhibit T cell activation and prevent immune responses. Hence, we hypothesized that co-delivering CTLA4Ig during AAV\/bNAb administration would prevent ADAs in primates. Six rhesus macaques (RMs) were treated intramuscularly with AAV-1 vectors encoding \u201crhesusized\u201d (rh) versions of the bNAbs 3BNC117 (IgG1) and 10-1074 (IgG2). The experimental monkeys (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 3) were dosed intravenously with 20 mg\/kg of rh-CTLA4Ig on days 0, 2, 7, and 14, while the control animals (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    = 3) did not receive any additional intervention. The experimental monkeys mounted ADAs that inhibited bNAb expression, albeit at different rates for rh-3BNC117-IgG1 (66%) and rh-10-1074-IgG2 (33%). In the control group, the incidence of ADAs leading to loss of bNAb expression was 100% for rh-3BNC117-IgG1 and 0% for rh-10-1074-IgG2. There was no significant difference between the groups in their cumulative levels of ADAs or bNAb expression measured over 20 weeks. Despite the development of ADAs against rh-3BNC117-IgG1 in five out of six animals, and in one out of six against rh-10-1074-IgG2, macaques in both groups exhibited minimal T cell responses to both bNAbs. AAV-1 capsid-specific CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells trended higher in the control animals. In conclusion, a short course rh-CTLA4Ig did not significantly reduce the immunogenicity of AAV-encoded bNAbs in RMs. Although our study was not powered to detect marginal effects, robust improvements in AAV-driven expression of hypermutated HIV-1 bNAbs may require combination approaches, such as multiple co-stimulation blockers, pharmacological immunosuppression, and\/or muscle-specific promoters.\n                  <\/jats:p>","DOI":"10.1177\/08892229251370763","type":"journal-article","created":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T19:33:45Z","timestamp":1761248025000},"page":"567-579","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":3,"title":["The Immunogenicity of AAV-Encoded HIV-1 bNAbs in Rhesus Macaques Is Unaffected by a Short Course of the Immunomodulator CTLA4Ig"],"prefix":"10.1177","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4338-4660","authenticated-orcid":false,"given":"Patricia A.","family":"Hahn","sequence":"first","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation &amp; Technology, Jupiter, Florida, USA."},{"name":"The Skaggs Graduate School, The Scripps Research Institute, Jupiter, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddhartha","family":"Shandilya","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation &amp; Technology, Jupiter, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas A.B.","family":"da Costa","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation &amp; Technology, Jupiter, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4492-0531","authenticated-orcid":false,"given":"Laura C.F.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation &amp; Technology, Jupiter, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"O\u2019Hagan","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation &amp; Technology, Jupiter, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Liang","sequence":"additional","affiliation":[{"name":"Nonhuman Primate Reagent Resource, UMass Chan Medical School, Worcester, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Engelman","sequence":"additional","affiliation":[{"name":"Nonhuman Primate Reagent Resource, UMass Chan Medical School, Worcester, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Gardner","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Disease, Emory School of Medicine, Atlanta, Georgia, USA."},{"name":"Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, Georgia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangping","family":"Gao","sequence":"additional","affiliation":[{"name":"Horae Gene Therapy Center, University of Massachusetts Medical School, Worcester, Massachusetts, USA."},{"name":"Department of Microbiology and Physiological Systems, University of Massachusetts Chan Medical School, Worcester, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian P.","family":"Fuchs","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine, University of Miami, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose M.","family":"Martinez-Navio","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine, University of Miami, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald C.","family":"Desrosiers","sequence":"additional","affiliation":[{"name":"Department of Pathology &amp; Laboratory Medicine, University of Miami, Miami, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir","family":"Ardeshir","sequence":"additional","affiliation":[{"name":"Tulane National Primate Research Center, Tulane University, Covington, Louisiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diogo M.","family":"Magnani","sequence":"additional","affiliation":[{"name":"Nonhuman Primate Reagent Resource, UMass Chan Medical School, Worcester, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio A.","family":"Martins","sequence":"additional","affiliation":[{"name":"Department of Immunology and Microbiology, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation &amp; Technology, Jupiter, Florida, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,20]]},"reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10844"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature14411"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad5752"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0531-2"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01815-1"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04597-1"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-022-04797-9"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.08.023"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-019-0012-9"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00176"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/mtm.2016.68"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.02.005"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.00449"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2015.191"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3018(19)30003-7"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-01762-x"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.165.2.302"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/381434a0"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1323143"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.178.5.1801"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1097\/MOT.0000000000000656"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035075"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050524"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60998-8"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.12460"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.4161\/mabs.23976"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0260954"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature13612"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0018556"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.1099\/0022-1317-72-11-2727"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.674242"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005090"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2019.01.004"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600682"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2012.04.082"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2011.00199"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1111\/jth.14757"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.mt.6300123"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2017.022"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtm.2020.03.008"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.179.10.6494"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.38982"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.8178155"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318281111"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1038\/16717"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2567.2008.02991.x"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.3899\/jrheum.141288"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.13377"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-065X.2009.00782.x"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.7.3348"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.3.1245"},{"key":"e_1_3_4_53_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34477-1"},{"key":"e_1_3_4_54_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.abb9283"}],"updated-by":[{"DOI":"10.1177\/08892229251380258","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000}}],"container-title":["AIDS Research and Human Retroviruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/08892229251370763","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/08892229251370763","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/08892229251370763","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T09:20:52Z","timestamp":1787131252000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/08892229251370763"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,20]]},"references-count":53,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12,1]]}},"alternative-id":["10.1177\/08892229251370763"],"URL":"https:\/\/doi.org\/10.1177\/08892229251370763","relation":{},"ISSN":["0889-2229","1931-8405"],"issn-type":[{"value":"0889-2229","type":"print"},{"value":"1931-8405","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,20]]}}}