Autologous neutralizing antibodies and polyfunctional T cells contribute to long-term HIV-1 post-intervention control
| Title: | Autologous neutralizing antibodies and polyfunctional T cells contribute to long-term HIV-1 post-intervention control |
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| Authors: | Fisher, Katie; Garcia, Mauro A.; Frattari, Giacomo S.; Naasz, Chloé; Zhuo, Junlin; Rosás-Umbert, Miriam; Dietz, Lisa L.; Juhl, Anna Karina; Falling Iversen, Emma; Olesen, Rikke; Schleimann, Mariane H.; Pahus, Marie H.; Johansen, Isik S.; Henderson, Merle; Carrere, Leah; Roseto, Isabelle; Gao, Ce; Yu, Xu G.; Fray, Emily J.; Aydin, Beril; Lubbeck, Donald; Lai, Jun; Simonetti, Francesco R.; Danesh, Ali; Miller, Itzayana; Mendoza, Pilar; Niessl, Julia; Gaebler, Christian; Seaman, Michael S.; Kaufmann, Daniel E.; Lehmann, Clara; Gruell, Henning; Klein, Florian; Caskey, Marina; Nussenzweig, Michel C.; Tolstrup, Martin; Jones, R. Brad; Gunst, Jesper D.; Siliciano, Janet D.; Lichterfeld, Mathias; Siliciano, Robert F.; Søgaard, Ole S. |
| Source: | Fisher, K, Garcia, M A, Frattari, G S, Naasz, C, Zhuo, J, Rosás-Umbert, M, Dietz, L L, Juhl, A K, Falling Iversen, E, Olesen, R, Schleimann, M H, Pahus, M H, Johansen, I S, Henderson, M, Carrere, L, Roseto, I, Gao, C, Yu, X G, Fray, E J, Aydin, B, Lubbeck, D, Lai, J, Simonetti, F R, Danesh, A, Miller, I, Mendoza, P, Niessl, J, Gaebler, C, Seaman, M S, Kaufmann, D E, Lehmann, C, Gruell, H, Klein, F, Caskey, M, Nussenzweig, M C, Tolstrup, M, Jones, R B, Gunst, J D, Siliciano, J D, Lichterfeld, M, Siliciano, R .... |
| Publication Year: | 2026 |
| Collection: | Aarhus University: Research |
| Description: | Antiretroviral therapy (ART) interruption typically leads to rapid HIV-1 viral rebound in people with HIV-1. To develop an HIV-1 cure, insight into immunological mechanisms capable of preventing HIV-1 viral rebound is urgently needed. Here, we describe three exceptional post-intervention controllers (PICs) who maintained ART-free virological control for >6.5 years (ongoing), >7.5 years (ongoing) and 2.5 years following administration of broadly neutralizing antibodies. PICs had quantifiable genetically intact/inducible infectious proviral reservoirs that were increasingly clonal and located in nongenic/centromeric chromosomal regions, indicating immune-mediated selection. Potent autologous neutralizing antibodies and polyfunctional HIV-1-specific CD4 + and CD8 + T cell responses, pre-programmed for antigen response, were present before, and persisted during, ART interruption. In one PIC, viral rebound following 2.5 years of ART-free control was associated with accumulated viral mutations that resulted in escape from neutralizing antibody and T cell responses. Collectively, our findings support developing HIV-1 curative strategies aimed at enhancing pre-existing adaptive immune responses. |
| Document Type: | article in journal/newspaper |
| Language: | English |
| ISSN: | 1529-2908; 1529-2916 |
| Relation: | info:eu-repo/semantics/altIdentifier/pmid/41776101; info:eu-repo/semantics/altIdentifier/pissn/1529-2908; info:eu-repo/semantics/altIdentifier/eissn/1529-2916 |
| DOI: | 10.1038/s41590-026-02448-z |
| Availability: | https://pure.au.dk/portal/en/publications/bd309f9f-9c0f-4d70-8028-c9172a91647c; https://doi.org/10.1038/s41590-026-02448-z; https://www.scopus.com/pages/publications/105032159036 |
| Rights: | info:eu-repo/semantics/openAccess ; http://creativecommons.org/licenses/by/4.0/ |
| Accession Number: | edsbas.EE0BC60B |
| Database: | BASE |