{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T22:58:33Z","timestamp":1792277913937,"version":"4.4.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1009738","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000}}],"reference-count":96,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T00:00:00Z","timestamp":1626739200000},"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":["P51-OD011092"],"award-info":[{"award-number":["P51-OD011092"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"national institutes of health","doi-asserted-by":"publisher","award":["R01-HD080459"],"award-info":[{"award-number":["R01-HD080459"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21-AI114433"],"award-info":[{"award-number":["R21-AI114433"]}],"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":["R01-AI145038"],"award-info":[{"award-number":["R01-AI145038"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01-CA253215"],"award-info":[{"award-number":["R01-CA253215"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Center for AIDS Research UCLA","award":["AI028697"],"award-info":[{"award-number":["AI028697"]}]},{"DOI":"10.13039\/100010296","name":"James B. Pendleton Charitable Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010296","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002214","name":"McCarthy Family Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002214","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Broadly neutralizing antibodies (bNAbs) directed to HIV-1 have shown promise at suppressing viremia in animal models. However, the use of bNAbs for the central nervous system (CNS) infection is confounded by poor penetration of the blood brain barrier (BBB). Typically, antibody concentrations in the CNS are extremely low; with levels in cerebrospinal fluid (CSF) only 0.1% of blood concentrations. Using a novel nanotechnology platform, which we term nanocapsules, we show effective transportation of the human bNAb PGT121 across the BBB in infant rhesus macaques upon systemic administration up to 1.6% of plasma concentration. We demonstrate that a single dose of PGT121 encased in nanocapsules when delivered at 48h post-infection delays early acute infection with SHIV<jats:sub>SF162P3<\/jats:sub>in infants, with one of four animals demonstrating viral clearance. Importantly, the nanocapsule delivery of PGT121 improves suppression of SHIV infection in the CNS relative to controls.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009738","type":"journal-article","created":{"date-parts":[[2021,7,20]],"date-time":"2021-07-20T17:55:48Z","timestamp":1626803748000},"page":"e1009738","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Improved delivery of broadly neutralizing antibodies by nanocapsules suppresses SHIV infection in the CNS of infant rhesus macaques"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6127-6276","authenticated-orcid":true,"given":"Jing","family":"Wen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2378-0690","authenticated-orcid":true,"given":"Tracy","family":"Cheever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3238-6388","authenticated-orcid":true,"given":"Di","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason","family":"Reed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5293-4695","authenticated-orcid":true,"given":"John","family":"Mascola","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9192-0440","authenticated-orcid":true,"given":"Xuejun","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiping","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3564-6453","authenticated-orcid":true,"given":"Amarendra","family":"Pegu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonah B.","family":"Sacha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunfeng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Haigwood","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1199-2415","authenticated-orcid":true,"given":"Irvin S. Y.","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,20]]},"reference":[{"issue":"6","key":"ppat.1009738.ref001","doi-asserted-by":"crossref","first-page":"828","DOI":"10.7326\/0003-4819-107-6-828","article-title":"Evidence for early central nervous system involvement in the acquired immunodeficiency syndrome (AIDS) and other human immunodeficiency virus (HIV) infections. Studies with neuropsychologic testing and magnetic resonance imaging","volume":"107","author":"I Grant","year":"1987","journal-title":"Ann Intern Med"},{"issue":"6831","key":"ppat.1009738.ref002","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1038\/35073667","article-title":"Pathways to neuronal injury and apoptosis in HIV-associated dementia","volume":"410","author":"M Kaul","year":"2001","journal-title":"Nature"},{"issue":"4803","key":"ppat.1009738.ref003","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1126\/science.3646751","article-title":"Dual infection of the central nervous system by AIDS viruses with distinct cellular tropisms","volume":"236","author":"Y Koyanagi","year":"1987","journal-title":"Science"},{"issue":"5465","key":"ppat.1009738.ref004","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1126\/science.288.5465.439d","article-title":"HIV-associated dementia","volume":"288","author":"EO Major","year":"2000","journal-title":"Science"},{"issue":"2","key":"ppat.1009738.ref005","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/0042-6822(91)90072-J","article-title":"HIV-1 V3 domain variation in brain and spleen of children with AIDS: tissue-specific evolution within host-determined quasispecies","volume":"180","author":"LG Epstein","year":"1991","journal-title":"Virology"},{"issue":"11","key":"ppat.1009738.ref006","first-page":"1082","article-title":"HIV-1 env sequence variation in brain tissue of patients with AIDS-related neurologic disease","volume":"4","author":"S Pang","year":"1991","journal-title":"J Acquir Immune Defic Syndr (1988)"},{"issue":"2","key":"ppat.1009738.ref007","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1006\/viro.1993.1503","article-title":"V3 sequences of paired HIV-1 isolates from blood and cerebrospinal fluid cluster according to host and show variation related to the clinical stage of disease","volume":"196","author":"B Keys","year":"1993","journal-title":"Virology"},{"issue":"Suppl 1","key":"ppat.1009738.ref008","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1080\/753312746","article-title":"Region-specific distribution of human immunodeficiency virus type 1 long terminal repeats containing specific configurations of CCAAT\/enhancer-binding protein site II in brains derived from demented and nondemented patients","volume":"10","author":"TH Burdo","year":"2004","journal-title":"J Neurovirol"},{"issue":"7","key":"ppat.1009738.ref009","doi-asserted-by":"crossref","first-page":"4643","DOI":"10.1128\/jvi.68.7.4643-4649.1994","article-title":"Demented and nondemented patients with AIDS differ in brain-derived human immunodeficiency virus type 1 envelope sequences","volume":"68","author":"C Power","year":"1994","journal-title":"J Virol"},{"issue":"2","key":"ppat.1009738.ref010","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1097\/01.aids.0000198078.24584.21","article-title":"Progressive selection for neurovirulent genotypes in the brain of SIV-infected macaques","volume":"20","author":"T Babas","year":"2006","journal-title":"AIDS"},{"issue":"5","key":"ppat.1009738.ref011","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1128\/JVI.01863-09","article-title":"Compartmentalization and clonal amplification of HIV-1 variants in the cerebrospinal fluid during primary infection","volume":"84","author":"G Schnell","year":"2010","journal-title":"J Virol"},{"issue":"Pt 7","key":"ppat.1009738.ref012","doi-asserted-by":"crossref","first-page":"1872","DOI":"10.1093\/brain\/awl136","article-title":"Genetic attributes of cerebrospinal fluid-derived HIV-1 env","volume":"129","author":"SK Pillai","year":"2006","journal-title":"Brain"},{"issue":"1","key":"ppat.1009738.ref013","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s11904-014-0255-3","article-title":"Neuropathogenesis of HIV: from initial neuroinvasion to HIV-associated neurocognitive disorder (HAND)","volume":"12","author":"Z Zayyad","year":"2015","journal-title":"Curr HIV\/AIDS Rep"},{"issue":"5","key":"ppat.1009738.ref014","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1097\/QAD.0b013e3283437d2f","article-title":"Eradication of HIV from the brain: reasons for pause","volume":"25","author":"A Nath","year":"2011","journal-title":"AIDS"},{"issue":"1","key":"ppat.1009738.ref015","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/nrmicro.2015.5","article-title":"HIV reservoirs: what, where and how to target them","volume":"14","author":"MJ Churchill","year":"2016","journal-title":"Nat Rev Microbiol"},{"issue":"2","key":"ppat.1009738.ref016","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/s11904-015-0257-9","article-title":"The Potential of the CNS as a Reservoir for HIV-1 Infection: Implications for HIV Eradication.","volume":"12","author":"AF Fois","year":"2015","journal-title":"Curr Hiv-Aids Rep"},{"issue":"6","key":"ppat.1009738.ref017","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1097\/COH.0000000000000108","article-title":"Is the central nervous system a reservoir of HIV-1?","volume":"9","author":"LR Gray","year":"2014","journal-title":"Curr Opin Hiv Aids"},{"issue":"9","key":"ppat.1009738.ref018","doi-asserted-by":"crossref","first-page":"1430","DOI":"10.1038\/s41591-018-0130-7","article-title":"Early antiretroviral therapy limits SIV reservoir establishment to delay or prevent post-treatment viral rebound","volume":"24","author":"AA Okoye","year":"2018","journal-title":"Nat Med"},{"issue":"6","key":"ppat.1009738.ref019","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1002\/ana.22053","article-title":"Human immunodeficiency virus-associated neurocognitive disorders: Mind the gap","volume":"67","author":"JC McArthur","year":"2010","journal-title":"Ann Neurol"},{"issue":"5","key":"ppat.1009738.ref020","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/nrneurol.2016.53","article-title":"HIV-associated neurocognitive disorder\u2014pathogenesis and prospects for treatment","volume":"12","author":"D Saylor","year":"2016","journal-title":"Nat Rev Neurol"},{"issue":"12","key":"ppat.1009738.ref021","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1086\/657342","article-title":"HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment","volume":"202","author":"A Eden","year":"2010","journal-title":"J Infect Dis"},{"issue":"1","key":"ppat.1009738.ref022","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S1044-7431(03)00171-4","article-title":"HIV-1 Tat protein upregulates inflammatory mediators and induces monocyte invasion into the brain","volume":"24","author":"H Pu","year":"2003","journal-title":"Mol Cell Neurosci"},{"key":"ppat.1009738.ref023","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.nbd.2012.08.007","article-title":"Astrocytic expression of HIV-1 Nef impairs spatial and recognition memory","volume":"49","author":"G Chompre","year":"2013","journal-title":"Neurobiol Dis"},{"issue":"2","key":"ppat.1009738.ref024","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.virol.2004.08.024","article-title":"Human immunodeficiency virus type 1 Nef protein mediates neural cell death: a neurotoxic role for IP-10","volume":"329","author":"G van Marle","year":"2004","journal-title":"Virology"},{"issue":"10","key":"ppat.1009738.ref025","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/ncpneuro0303","article-title":"Therapy Insight: CNS manifestations of HIV-associated immune reconstitution inflammatory syndrome.","volume":"2","author":"DJ Riedel","year":"2006","journal-title":"Nat Clin Pract Neurol"},{"issue":"1\u20132","key":"ppat.1009738.ref026","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0022-510X(02)00207-1","article-title":"The role of macrophage\/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis","volume":"202","author":"A Minagar","year":"2002","journal-title":"J Neurol Sci"},{"issue":"2","key":"ppat.1009738.ref027","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/infdis\/jis326","article-title":"Central nervous system viral invasion and inflammation during acute HIV infection","volume":"206","author":"V Valcour","year":"2012","journal-title":"J Infect Dis"},{"issue":"4","key":"ppat.1009738.ref028","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1007\/s11481-009-9174-2","article-title":"CNS inflammation and macrophage\/microglial biology associated with HIV-1 infection","volume":"4","author":"A Yadav","year":"2009","journal-title":"J Neuroimmune Pharmacol."},{"issue":"3","key":"ppat.1009738.ref029","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1097\/COH.0b013e32835fc601","article-title":"Where does HIV hide? A focus on the central nervous system","volume":"8","author":"M Churchill","year":"2013","journal-title":"Curr Opin Hiv Aids"},{"issue":"2","key":"ppat.1009738.ref030","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/j.1750-3639.2003.tb00014.x","article-title":"Detection of HIV-1 DNA in microglia\/macrophages, astrocytes and neurons isolated from brain tissue with HIV-1 encephalitis by laser capture microdissection","volume":"13","author":"G Trillo-Pazos","year":"2003","journal-title":"Brain Pathol"},{"issue":"3","key":"ppat.1009738.ref031","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0165-0173(94)00015-H","article-title":"Microglia: intrinsic immuneffector cell of the brain","volume":"20","author":"J Gehrmann","year":"1995","journal-title":"Brain Res Brain Res Rev"},{"issue":"3","key":"ppat.1009738.ref032","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1016\/j.nbd.2009.02.015","article-title":"Increased activation of Iba1+ microglia in pediatric epilepsy patients with Rasmussen\u2019s encephalitis compared with cortical dysplasia and tuberous sclerosis complex","volume":"34","author":"M Wirenfeldt","year":"2009","journal-title":"Neurobiol Dis"},{"issue":"11","key":"ppat.1009738.ref033","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1016\/j.neurobiolaging.2007.04.013","article-title":"Neocortical glial cell numbers in human brains","volume":"29","author":"DP Pelvig","year":"2008","journal-title":"Neurobiol Aging"},{"issue":"8","key":"ppat.1009738.ref034","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1038\/nm.1967","article-title":"Vector-mediated gene transfer engenders long-lived neutralizing activity and protection against SIV infection in monkeys","volume":"15","author":"PR Johnson","year":"2009","journal-title":"Nat Med"},{"issue":"7541","key":"ppat.1009738.ref035","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/nature14264","article-title":"AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges","volume":"519","author":"MR Gardner","year":"2015","journal-title":"Nature"},{"issue":"7524","key":"ppat.1009738.ref036","doi-asserted-by":"crossref","first-page":"642","DOI":"10.1038\/nature13612","article-title":"Enhanced neonatal Fc receptor function improves protection against primate SHIV infection","volume":"514","author":"SY Ko","year":"2014","journal-title":"Nature"},{"issue":"7475","key":"ppat.1009738.ref037","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1038\/nature12744","article-title":"Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys","volume":"503","author":"DH Barouch","year":"2013","journal-title":"Nature"},{"issue":"5","key":"ppat.1009738.ref038","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.cell.2014.07.043","article-title":"Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice","volume":"158","author":"A Halper-Stromberg","year":"2014","journal-title":"Cell"},{"issue":"3","key":"ppat.1009738.ref039","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/nm.3471","article-title":"Vectored immunoprophylaxis protects humanized mice from mucosal HIV transmission","volume":"20","author":"AB Balazs","year":"2014","journal-title":"Nat Med"},{"issue":"4","key":"ppat.1009738.ref040","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/s41591-019-0412-8","article-title":"Broadly neutralizing anti-HIV-1 monoclonal antibodies in the clinic","volume":"25","author":"M Caskey","year":"2019","journal-title":"Nat Med"},{"issue":"2","key":"ppat.1009738.ref041","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/nm.4268","article-title":"Antibody 10\u20131074 suppresses viremia in HIV-1-infected individuals","volume":"23","author":"M Caskey","year":"2017","journal-title":"Nat Med"},{"issue":"9","key":"ppat.1009738.ref042","doi-asserted-by":"crossref","first-page":"2311","DOI":"10.1084\/jem.20180936","article-title":"Relationship between latent and rebound viruses in a clinical trial of anti-HIV-1 antibody 3BNC117","volume":"215","author":"YZ Cohen","year":"2018","journal-title":"J Exp Med"},{"issue":"7613","key":"ppat.1009738.ref043","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1038\/nature18929","article-title":"HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption","volume":"535","author":"JF Scheid","year":"2016","journal-title":"Nature"},{"issue":"11","key":"ppat.1009738.ref044","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1038\/s41591-018-0186-4","article-title":"Safety and antiviral activity of combination HIV-1 broadly neutralizing antibodies in viremic individuals","volume":"24","author":"Y Bar-On","year":"2018","journal-title":"Nat Med"},{"issue":"7724","key":"ppat.1009738.ref045","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/s41586-018-0531-2","article-title":"Combination therapy with anti-HIV-1 antibodies maintains viral suppression","volume":"561","author":"P Mendoza","year":"2018","journal-title":"Nature"},{"issue":"4","key":"ppat.1009738.ref046","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1038\/nm.4063","article-title":"Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques","volume":"22","author":"AJ Hessell","year":"2016","journal-title":"Nat Med"},{"issue":"1","key":"ppat.1009738.ref047","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1038\/s41467-019-13972-y","article-title":"Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity","volume":"11","author":"MB Shapiro","year":"2020","journal-title":"Nat Commun"},{"issue":"3","key":"ppat.1009738.ref048","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1128\/JVI.02454-15","article-title":"Human Immunodeficiency Virus Type 1 Monoclonal Antibodies Suppress Acute Simian-Human Immunodeficiency Virus Viremia and Limit Seeding of Cell-Associated Viral Reservoirs","volume":"90","author":"DL Bolton","year":"2016","journal-title":"J Virol"},{"issue":"7646","key":"ppat.1009738.ref049","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/nature21435","article-title":"Early antibody therapy can induce long-lasting immunity to SHIV","volume":"543","author":"Y Nishimura","year":"2017","journal-title":"Nature"},{"issue":"1","key":"ppat.1009738.ref050","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s11904-019-00428-7","article-title":"HIV Eradication Strategies: Implications for the Central Nervous System","volume":"16","author":"RT Veenhuis","year":"2019","journal-title":"Curr HIV\/AIDS Rep"},{"issue":"5","key":"ppat.1009738.ref051","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1182\/blood-2012-07-440974","article-title":"Multicenter phase 1 trial of intraventricular immunochemotherapy in recurrent CNS lymphoma","volume":"121","author":"JL Rubenstein","year":"2013","journal-title":"Blood"},{"issue":"11","key":"ppat.1009738.ref052","doi-asserted-by":"crossref","first-page":"1978","DOI":"10.1093\/annonc\/mdn654","article-title":"High-dose intrathecal trastuzumab for leptomeningeal metastases secondary to HER-2 overexpressing breast cancer","volume":"19","author":"O Mir","year":"2008","journal-title":"Ann Oncol"},{"issue":"6","key":"ppat.1009738.ref053","first-page":"753","article-title":"Intraventricular treatment of relapsed central nervous system lymphoma with the anti-CD20 antibody rituximab","volume":"89","author":"H Schulz","year":"2004","journal-title":"Haematologica"},{"issue":"11","key":"ppat.1009738.ref054","doi-asserted-by":"crossref","first-page":"1350","DOI":"10.1200\/JCO.2006.09.7311","article-title":"Phase I study of intraventricular administration of rituximab in patients with recurrent CNS and intraocular lymphoma","volume":"25","author":"JL Rubenstein","year":"2007","journal-title":"J Clin Oncol"},{"issue":"5","key":"ppat.1009738.ref055","first-page":"1373","article-title":"Application of intrathecal trastuzumab (Herceptintrade mark) for treatment of meningeal carcinomatosis in HER2-overexpressing metastatic breast cancer","volume":"15","author":"HJ Stemmler","year":"2006","journal-title":"Oncol Rep"},{"issue":"1","key":"ppat.1009738.ref056","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/s10549-013-2525-y","article-title":"Intrathecal administration of trastuzumab for the treatment of meningeal carcinomatosis in HER2-positive metastatic breast cancer: a systematic review and pooled analysis","volume":"139","author":"F Zagouri","year":"2013","journal-title":"Breast Cancer Res Treat"},{"issue":"2","key":"ppat.1009738.ref057","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s11060-006-9217-y","article-title":"Intrathecal anti-CD20 antibody: an effective and safe treatment for leptomeningeal lymphoma","volume":"81","author":"G Antonini","year":"2007","journal-title":"J Neurooncol"},{"issue":"4","key":"ppat.1009738.ref058","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1002\/pbc.21297","article-title":"Intrathecal rituximab treatment for pediatric post-transplant lymphoproliferative disorder of the central nervous system","volume":"50","author":"G van de Glind","year":"2008","journal-title":"Pediatr Blood Cancer"},{"issue":"3","key":"ppat.1009738.ref059","doi-asserted-by":"crossref","first-page":"503","DOI":"10.3109\/10428194.2012.718342","article-title":"Intrathecal therapy with rituximab in central nervous system involvement of post-transplant lymphoproliferative disorder","volume":"54","author":"K Czyzewski","year":"2013","journal-title":"Leuk Lymphoma"},{"key":"ppat.1009738.ref060","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s40425-015-0084-y","article-title":"Intrathecal trastuzumab: immunotherapy improves the prognosis of leptomeningeal metastases in HER-2+ breast cancer patient","volume":"3","author":"NT Lu","year":"2015","journal-title":"J Immunother Cancer"},{"issue":"9","key":"ppat.1009738.ref061","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/nbt.3330","article-title":"Principles of nanoparticle design for overcoming biological barriers to drug delivery","volume":"33","author":"E Blanco","year":"2015","journal-title":"Nat Biotechnol"},{"key":"ppat.1009738.ref062","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.addr.2013.08.008","article-title":"Drug delivery to the central nervous system by polymeric nanoparticles: what do we know?","volume":"71","author":"J. Kreuter","year":"2014","journal-title":"Adv Drug Deliv Rev"},{"issue":"4","key":"ppat.1009738.ref063","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1007\/s12274-016-0991-3","article-title":"Phosphorylcholine polymer nanocapsules prolong the circulation time and reduce the immunogenicity of therapeutic proteins","volume":"9","author":"S Liang","year":"2016","journal-title":"Nano Res"},{"key":"ppat.1009738.ref064","article-title":"Enhanced Delivery of Rituximab Into Brain and Lymph Nodes Using Timed-Release Nanocapsules in Non-Human Primates","volume":"10","author":"M Qin","year":"2020","journal-title":"Front Immunol"},{"issue":"33","key":"ppat.1009738.ref065","article-title":"Efficient Delivery of Nerve Growth Factors to the Central Nervous System for Neural Regeneration","volume":"31","author":"D Xu","year":"2019","journal-title":"Adv Mater"},{"issue":"18","key":"ppat.1009738.ref066","article-title":"A Bioinspired Platform for Effective Delivery of Protein Therapeutics to the Central Nervous System","volume":"31","author":"D Wu","year":"2019","journal-title":"Adv Mater"},{"issue":"19","key":"ppat.1009738.ref067","article-title":"Systemic Delivery of Monoclonal Antibodies to the Central Nervous System for Brain Tumor Therapy","volume":"31","author":"L Han","year":"2019","journal-title":"Adv Mater"},{"issue":"9","key":"ppat.1009738.ref068","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1038\/s41551-019-0434-z","article-title":"Sustained delivery and molecular targeting of a therapeutic monoclonal antibody to metastases in the central nervous system of mice","volume":"3","author":"J Wen","year":"2019","journal-title":"Nat Biomed Eng"},{"issue":"3","key":"ppat.1009738.ref069","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1097\/COH.0000000000000152","article-title":"Animal models in HIV-1 protection and therapy","volume":"10","author":"AJ Hessell","year":"2015","journal-title":"Curr Opin Hiv Aids"},{"issue":"12","key":"ppat.1009738.ref070","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/j.addr.2004.07.011","article-title":"Principles and applicability of CSF sampling for the assessment of CNS drug delivery and pharmacodynamics","volume":"56","author":"DD Shen","year":"2004","journal-title":"Adv Drug Deliv Rev"},{"issue":"1","key":"ppat.1009738.ref071","doi-asserted-by":"crossref","first-page":"46","DOI":"10.2174\/138920008783331077","article-title":"CSF as a surrogate for assessing CNS exposure: An industrial perspective","volume":"9","author":"JH Lin","year":"2008","journal-title":"Curr Drug Metab"},{"issue":"2","key":"ppat.1009738.ref072","first-page":"143","article-title":"Detection of interferon-gamma and IL-6 producing cells in cerebrospinal fluid cells in the central nervous system infectious diseases using immunocytochemistry","volume":"32","author":"S Nakamura","year":"1992","journal-title":"Rinsho Shinkeigaku"},{"key":"ppat.1009738.ref073","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S0072-9752(07)85017-2","article-title":"Cerebrospinal fluid markers in central nervous system HIV infection and AIDS dementia complex","volume":"85","author":"P Cinque","year":"2007","journal-title":"Handb Clin Neurol"},{"issue":"Suppl","key":"ppat.1009738.ref074","doi-asserted-by":"crossref","first-page":"S58","DOI":"10.1002\/ana.410230716","article-title":"Distinct biological and serological properties of human immunodeficiency viruses from the brain","volume":"23","author":"C Cheng-Mayer","year":"1988","journal-title":"Ann Neurol"},{"issue":"6617","key":"ppat.1009738.ref075","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1038\/385645a0","article-title":"CCR3 and CCR5 are co-receptors for HIV-1 infection of microglia","volume":"385","author":"J He","year":"1997","journal-title":"Nature"},{"issue":"1","key":"ppat.1009738.ref076","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1007\/s13365-013-0229-z","article-title":"Giant cell encephalitis and microglial infection with mucosally transmitted simian-human immunodeficiency virus SHIVSF162P3N in rhesus macaques","volume":"20","author":"C Harbison","year":"2014","journal-title":"J Neurovirol"},{"issue":"46","key":"ppat.1009738.ref077","doi-asserted-by":"crossref","first-page":"18921","DOI":"10.1073\/pnas.1214785109","article-title":"Highly potent HIV-specific antibody neutralization in vitro translates into effective protection against mucosal SHIV challenge in vivo","volume":"109","author":"B Moldt","year":"2012","journal-title":"P Natl Acad Sci USA"},{"issue":"1","key":"ppat.1009738.ref078","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/0165-0270(83)90050-X","article-title":"Evans blue fluorescence: quantitative and morphological evaluation of vascular permeability in animal tissues","volume":"8","author":"A Saria","year":"1983","journal-title":"J Neurosci Methods"},{"issue":"7","key":"ppat.1009738.ref079","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.4049\/jimmunol.1502252","article-title":"IgG Binding Characteristics of Rhesus Macaque FcgammaR","volume":"197","author":"YN Chan","year":"2016","journal-title":"J Immunol"},{"key":"ppat.1009738.ref080","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.expneurol.2014.06.019","article-title":"Complement emerges as a masterful regulator of CNS homeostasis, neural synaptic plasticity and cognitive function","volume":"261","author":"DC Mastellos","year":"2014","journal-title":"Exp Neurol"},{"issue":"5","key":"ppat.1009738.ref081","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1038\/nrn3722","article-title":"Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease","volume":"15","author":"M Prinz","year":"2014","journal-title":"Nat Rev Neurosci"},{"issue":"4","key":"ppat.1009738.ref082","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1159\/000163657","article-title":"Antibody-Mediated Tumor-Cytotoxicity of Microglia","volume":"59","author":"A Sutter","year":"1991","journal-title":"Pathobiology."},{"issue":"1","key":"ppat.1009738.ref083","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cell.2014.06.008","article-title":"Sublime Microglia: Expanding Roles for the Guardians of the CNS","volume":"158","author":"MW Salter","year":"2014","journal-title":"Cell"},{"issue":"6","key":"ppat.1009738.ref084","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1016\/j.cell.2007.10.036","article-title":"The classical complement cascade mediates CNS synapse elimination","volume":"131","author":"B Stevens","year":"2007","journal-title":"Cell"},{"issue":"1\u20132","key":"ppat.1009738.ref085","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/S0162-3109(00)80302-1","article-title":"Complement components of the innate immune system in health and disease in the CNS","volume":"49","author":"P Gasque","year":"2000","journal-title":"Immunopharmacology"},{"issue":"7427","key":"ppat.1009738.ref086","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nature11604","article-title":"HIV therapy by a combination of broadly neutralizing antibodies in humanized mice","volume":"492","author":"F Klein","year":"2012","journal-title":"Nature"},{"issue":"41","key":"ppat.1009738.ref087","doi-asserted-by":"crossref","first-page":"16538","DOI":"10.1073\/pnas.1315295110","article-title":"HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice","volume":"110","author":"JA Horwitz","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"7109","key":"ppat.1009738.ref088","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1038\/nature05115","article-title":"PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression","volume":"443","author":"CL Day","year":"2006","journal-title":"Nature"},{"issue":"5","key":"ppat.1009738.ref089","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/j.it.2019.03.008","article-title":"Antibodies Tip the Balance Towards an HIV Cure","volume":"40","author":"NL Haigwood","year":"2019","journal-title":"Trends Immunol"},{"key":"ppat.1009738.ref090","first-page":"8141269","article-title":"Recent Advances in Assessing Immunogenicity of Therapeutic Proteins: Impact on Biotherapeutic Development","volume":"2016","author":"Y Lu","year":"2016","journal-title":"J Immunol Res"},{"issue":"3","key":"ppat.1009738.ref091","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1016\/j.ymthe.2019.01.004","article-title":"Anti-drug Antibody Responses Impair Prophylaxis Mediated by AAV-Delivered HIV-1 Broadly Neutralizing Antibodies","volume":"27","author":"MR Gardner","year":"2019","journal-title":"Mol Ther"},{"issue":"3","key":"ppat.1009738.ref092","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/j.immuni.2019.02.005","article-title":"Adeno-Associated Virus Delivery of Anti-HIV Monoclonal Antibodies Can Drive Long-Term Virologic Suppression","volume":"50","author":"JM Martinez-Navio","year":"2019","journal-title":"Immunity"},{"issue":"7","key":"ppat.1009738.ref093","doi-asserted-by":"crossref","first-page":"e99881","DOI":"10.1371\/journal.pone.0099881","article-title":"Transplanting supersites of HIV-1 vulnerability","volume":"9","author":"T Zhou","year":"2014","journal-title":"PLoS One"},{"key":"ppat.1009738.ref094","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/978-1-62703-520-0_3","article-title":"Microglia isolation from adult mouse brain","volume":"1041","author":"JK Lee","year":"2013","journal-title":"Methods Mol Biol"},{"issue":"5\u20136","key":"ppat.1009738.ref095","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1111\/j.1600-0684.2005.00128.x","article-title":"Highly sensitive SIV plasma viral load assay: practical considerations, realistic performance expectations, and application to reverse engineering of vaccines for AIDS","volume":"34","author":"AN Cline","year":"2005","journal-title":"J Med Primatol"},{"issue":"7348","key":"ppat.1009738.ref096","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1038\/nature10003","article-title":"Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine","volume":"473","author":"SG Hansen","year":"2011","journal-title":"Nature"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1009738","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2021,7,30]],"date-time":"2021-07-30T00:00:00Z","timestamp":1627603200000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009738","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,6]],"date-time":"2023-11-06T08:08:05Z","timestamp":1699258085000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009738"}},"subtitle":[],"editor":[{"given":"Guido","family":"Silvestri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,7,20]]},"references-count":96,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1009738","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1009738","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,20]]}}}