{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T10:28:53Z","timestamp":1763375333362,"version":"3.45.0"},"reference-count":41,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2025,11,15]],"date-time":"2025-11-15T00:00:00Z","timestamp":1763164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>This study investigated the protective efficacy of two distinct combinations of three recombinant adeno-associated virus serotype 9 (rAAV9) vectors encoding broadly neutralizing antibodies against HIV-1\u2014CombiMab-1 and CombiMab-2\u2014in mice humanized with primary CD4+ T-lymphocytes. We demonstrated that mice preventively treated with CombiMab-1 or CombiMab-2 did not develop viremia and maintained human CD4+ T-lymphocyte counts following viral challenge, in contrast to control animals. These results demonstrate the significant protective capacity of CombiMab-1 and CombiMab-2 against HIV-1 challenge.<\/jats:p>","DOI":"10.3390\/ijms262211051","type":"journal-article","created":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T10:24:58Z","timestamp":1763375098000},"page":"11051","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Triple rAAV9 Vector Combinations Encoding Broadly Neutralizing Antibodies Effectively Suppress HIV-1 Infection in Humanized Mice"],"prefix":"10.3390","volume":"26","author":[{"given":"Danila S.","family":"Leontyev","sequence":"first","affiliation":[{"name":"Centre for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2304-7787","authenticated-orcid":false,"given":"Felix A.","family":"Urusov","sequence":"additional","affiliation":[{"name":"Centre for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dina V.","family":"Glazkova","sequence":"additional","affiliation":[{"name":"Centre for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2646-9774","authenticated-orcid":false,"given":"Boris V.","family":"Belugin","sequence":"additional","affiliation":[{"name":"Centre for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasia A.","family":"Mitiushina","sequence":"additional","affiliation":[{"name":"Centre for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1527-949X","authenticated-orcid":false,"given":"Galina M.","family":"Tsyganova","sequence":"additional","affiliation":[{"name":"Centre for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7942-8004","authenticated-orcid":false,"given":"Sergey M.","family":"Yudin","sequence":"additional","affiliation":[{"name":"Centre for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3250-6498","authenticated-orcid":false,"given":"Elena V.","family":"Bogoslovskaya","sequence":"additional","affiliation":[{"name":"Centre for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"German A.","family":"Shipulin","sequence":"additional","affiliation":[{"name":"Centre for Strategic Planning and Management of Biomedical Health Risks, Federal Medical Biological Agency, 119992 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,15]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, June 09). HIV and AIDS. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hiv-aids."},{"key":"ref_2","unstructured":"UNAIDS (2025, June 09). Global HIV & AIDS Statistics\u2014Fact Sheet. Available online: https:\/\/www.unaids.org\/en\/resources\/fact-sheet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1038\/ni.3152","article-title":"HIV reservoirs as obstacles and opportunities for an HIV cure","volume":"16","author":"Chun","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1089\/aid.2011.0017","article-title":"Eradication therapies for HIV Infection: Time to begin again","volume":"27","author":"Margolis","year":"2011","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Tebas, P. (2025). Future of bNAbs in HIV Treatment. Curr. HIV\/AIDS Rep., 22.","DOI":"10.1007\/s11904-025-00744-1"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Thavarajah, J.J., H\u00f8nge, B.L., and Wejse, C.M. (2024). The Use of Broadly Neutralizing Antibodies (bNAbs) in HIV-1 Treatment and Prevention. Viruses, 16.","DOI":"10.20944\/preprints202405.0383.v1"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3534","DOI":"10.1038\/s41591-024-03247-5","article-title":"Safety and antiviral effect of a triple combination of HIV-1 broadly neutralizing antibodies: A phase 1\/2a trial","volume":"30","author":"Julg","year":"2024","journal-title":"Nat. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1146\/annurev-immunol-041015-055515","article-title":"Broadly Neutralizing Antibodies to HIV and Their Role in Vaccine Design","volume":"34","author":"Burton","year":"2016","journal-title":"Annu. Rev. Immunol."},{"key":"ref_9","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":"Lu","year":"2014","journal-title":"Cell"},{"key":"ref_10","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":"Mendoza","year":"2018","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1126\/science.aaf1279","article-title":"Enhanced clearance of HIV-1-infected cells by broadly neutralizing antibodies against HIV-1 in vivo","volume":"352","author":"Lu","year":"2016","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kochina, E.A., Urusov, F.A., Kruglov, A.A., Glazkova, D.V., Shipulin, G.A., and Bogoslovskaya, E.V. (2022). Double and triple combinations of broadly neutralizing antibodies provide efficient neutralization of all HIV-1 strains from the global panel. Viruses, 14.","DOI":"10.3390\/v14091910"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Wang, J.H., Gessler, D.J., Zhan, W., Gallagher, T.L., and Gao, G. (2024). Adeno-associated virus as a delivery vector for gene therapy of human diseases. Sig. Transduct. Target. Ther., 9.","DOI":"10.1038\/s41392-024-01780-w"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1007\/s00109-020-02034-2","article-title":"Evolving AAV-delivered therapeutics towards ultimate cures","volume":"99","author":"He","year":"2021","journal-title":"J. Mol. Med."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Fuchs, S.P., and Desrosiers, R.C. (2016). Promise and problems associated with the use of recombinant AAV for the delivery of anti-HIV antibodies. Mol. Ther. Methods Clin. Dev., 3.","DOI":"10.1038\/mtm.2016.68"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Shipulin, G.A., Glazkova, D.V., Urusov, F.A., Belugin, B.V., Dontsova, V., Panova, A.V., Borisova, A.A., Tsyganova, G.M., and Bogoslovskaya, E.V. (2024). Triple Combinations of AAV9-Vectors Encoding Anti-HIV bNAbs Provide Long-Term In Vivo Expression of Human IgG Effectively Neutralizing Pseudoviruses from HIV-1 Global Panel. Viruses, 16.","DOI":"10.3390\/v16081296"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.1016\/j.immuni.2016.10.027","article-title":"Identification of a CD4-Binding-Site Antibody to HIV that Evolved Near-Pan Neutralization Breadth","volume":"45","author":"Huang","year":"2016","journal-title":"Immunity"},{"key":"ref_18","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":"Nishimura","year":"2017","journal-title":"Nature"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Williams, L.D., Ofek, G., Sch\u00e4tzle, S., McDaniel, J.R., Lu, X., Nicely, N.I., Wu, L., Lougheed, C.S., Bradley, T., and Louder, M.K. (2017). Potent and broad HIV-neutralizing antibodies in memory B cells and plasma. Sci. Immunol., 2.","DOI":"10.1126\/sciimmunol.aal2200"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"12669","DOI":"10.1128\/JVI.02213-14","article-title":"Enhanced Potency of a Broadly Neutralizing HIV-1 Antibody In Vitro Improves Protection against Lentiviral Infection In Vivo","volume":"88","author":"Rudicell","year":"2014","journal-title":"J. Virol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"17624","DOI":"10.1073\/pnas.1415789111","article-title":"Recombinant HIV envelope trimer selects for quaternary-dependent antibodies targeting the trimer apex","volume":"111","author":"Sok","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"312","DOI":"10.30895\/2221-996X-2024-24-3-312-321","article-title":"Study of the protective efficacy of CombiMab-2 against human immunodeficiency virus type 1 in mice humanised with CD4+ T-lymphocytes","volume":"24","author":"Leontyev","year":"2024","journal-title":"Biol. Prod. Prev. Diagn. Treat."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/nature10660","article-title":"Antibody-based protection against HIV infection by vectored immunoprophylaxis","volume":"481","author":"Balazs","year":"2011","journal-title":"Nature"},{"key":"ref_24","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":"Balazs","year":"2014","journal-title":"Nat. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1097\/MED.0b013e328337282f","article-title":"Humanized mouse models to study human diseases","volume":"17","author":"Brehm","year":"2010","journal-title":"Curr. Opin. Endocrinol. Diabetes Obes."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1038\/nri3311","article-title":"Humanized mice for immune system investigation: Progress, promise and challenges","volume":"12","author":"Shultz","year":"2012","journal-title":"Nat. Rev. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1111\/ajt.14116","article-title":"Novel Xenogeneic Graft-Versus-Host Disease Model for Investigating the Pathological Role of Human CD4+ or CD8+ T Cells Using Immunodeficient NOG Mice","volume":"17","author":"Ito","year":"2017","journal-title":"Am. J. Transplant."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Cattin, A., Pham, T., Dias, J., Ros\u00e1rio, N., Marchand, L., Volodina, O., Guimond, J., Patey, N., Li, Y., and B\u00e9land, K. (2025). Humanized Bone Marrow-Liver-Thymus Mice for Studying HIV-1 Persistence in Liver and Lung CD4+ T and Myeloid Cell Subsets during Antiretroviral Therapy. bioRxiv.","DOI":"10.1101\/2025.01.31.635552"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1038\/s41423-019-0347-5","article-title":"Conversion of effector CD4+ T cells to a CD8+ MHC II-recognizing lineage","volume":"18","author":"Robins","year":"2021","journal-title":"Cell. Mol. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.4049\/jimmunol.154.6.2678","article-title":"Analysis of the intra-epithelial lymphocyte compartment in SCID mice that received co-isogenic CD4+ T cells. Evidence that mature post-thymic CD4+ T cells can be induced to express CD8 alpha in vivo","volume":"154","author":"Morrissey","year":"1995","journal-title":"J. Immunol."},{"key":"ref_31","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":"Horwitz","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/COH.0000000000000600","article-title":"Broadly neutralizing antibodies for the treatment and prevention of HIV infection","volume":"15","author":"Caskey","year":"2020","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1111\/cei.12051","article-title":"Human T cells depend on functional calcineurin, tumour necrosis factor-\u03b1 and CD80\/CD86 for expansion and activation in mice","volume":"172","author":"Kvist","year":"2013","journal-title":"Clin. Exp. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lin, A., and Balazs, A.B. (2018). Adeno-Associated Virus Gene Delivery of Broadly Neutralizing Antibodies as Prevention and Therapy Against HIV-1. Retrovirology, 15.","DOI":"10.1186\/s12977-018-0449-7"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Walsh, S.R., and Seaman, M.S. (2021). Broadly Neutralizing Antibodies for HIV-1 Prevention. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.712122"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Chen, J., Liao, S., Xiao, Z., Pan, Q., Wang, X., Shen, K., Wang, S., Yang, L., Guo, F., and Liu, H. (2022). The development and improvement of immunodeficient mice and humanized immune system mouse models. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1007579"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Kim, J.T., Bresson-Tan, G., and Zack, J.A. (2023). Current Advances in Humanized Mouse Models for Studying NK Cells and HIV Infection. Microorganisms, 11.","DOI":"10.3390\/microorganisms11081984"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Boh\u00f3rquez, J.A., Adduri, S., Ansari, D., John, S., Florence, J., Adejare, O., Singh, G., Konduru, N.V., Jagannath, C., and Yi, G. (2024). A Novel Humanized Mouse Model for HIV and Tuberculosis Co-Infection Studies. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1395018"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/j.stemcr.2023.01.003","article-title":"Generation of Functional Human T Cell Development in NOD\/SCID\/IL2r\u03b3null Humanized Mice without Using Fetal Tissue: Application as a Model of HIV Infection and Persistence","volume":"18","author":"Colas","year":"2023","journal-title":"Stem Cell Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/s41586-022-04797-9","article-title":"Combination Anti-HIV Antibodies Provide Sustained Virological Suppression","volume":"606","author":"Sneller","year":"2022","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Terahara, K., Iwabuchi, R., and Tsunetsugu-Yokota, Y. (2021). Perspectives on Non-BLT Humanized Mouse Models for Studying HIV Pathogenesis and Therapy. Viruses, 13.","DOI":"10.3390\/v13050776"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/22\/11051\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T10:25:55Z","timestamp":1763375155000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/22\/11051"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,15]]},"references-count":41,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ijms262211051"],"URL":"https:\/\/doi.org\/10.3390\/ijms262211051","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,15]]}}}