Pub Date : 2026-02-09DOI: 10.1038/s41590-026-02446-1
Mikhail B Litinskiy, Bernardetta Nardelli, David M Hilbert, Bing He, Andras Schaffer, Paolo Casali, Andrea Cerutti
{"title":"Retraction Note: DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL.","authors":"Mikhail B Litinskiy, Bernardetta Nardelli, David M Hilbert, Bing He, Andras Schaffer, Paolo Casali, Andrea Cerutti","doi":"10.1038/s41590-026-02446-1","DOIUrl":"https://doi.org/10.1038/s41590-026-02446-1","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-09DOI: 10.1038/s41590-025-02398-y
Vasileios I Theofilou, David Fraser, Eleni Kanasi, Laurie Brenchley, Teresa Greenwell-Wild, Emmanuel E Adade, Alex M Valm, Iyadh Douagi, Yasmine Belkaid, Duy T Tran, Drake W Williams, Niki M Moutsopoulos
Immune responsiveness at barrier surfaces is tailored to the exposures of each tissue. In the oral mucosa, mechanisms by which a permeable epithelium coexists with diverse microbiota and maintains integrity during inflammatory pathology remain poorly understood. We compile a multiomics spatial map of this exposed mucosal microenvironment and uncover remarkable immune zonation with organization that is preserved even during inflammatory disease. At the tooth interface, we identify a dynamic epithelium underlined by a layer of neutrophils and a zone of antigen-presenting cell-lymphocyte aggregates. During disease, inflammatory zones expand and organize into immature tertiary lymphoid structures, suggesting local antibody production. Location-specific transcriptomes support a role for the stromal compartment in the spatial organization of immunity. This preserved immune zonation meets the demands for continuous protection of this vulnerable interface and suggests unique tissue-specific wiring of immunity at the human oral mucosal barrier.
{"title":"Distinct spatial organization governs oral mucosal immunity.","authors":"Vasileios I Theofilou, David Fraser, Eleni Kanasi, Laurie Brenchley, Teresa Greenwell-Wild, Emmanuel E Adade, Alex M Valm, Iyadh Douagi, Yasmine Belkaid, Duy T Tran, Drake W Williams, Niki M Moutsopoulos","doi":"10.1038/s41590-025-02398-y","DOIUrl":"https://doi.org/10.1038/s41590-025-02398-y","url":null,"abstract":"<p><p>Immune responsiveness at barrier surfaces is tailored to the exposures of each tissue. In the oral mucosa, mechanisms by which a permeable epithelium coexists with diverse microbiota and maintains integrity during inflammatory pathology remain poorly understood. We compile a multiomics spatial map of this exposed mucosal microenvironment and uncover remarkable immune zonation with organization that is preserved even during inflammatory disease. At the tooth interface, we identify a dynamic epithelium underlined by a layer of neutrophils and a zone of antigen-presenting cell-lymphocyte aggregates. During disease, inflammatory zones expand and organize into immature tertiary lymphoid structures, suggesting local antibody production. Location-specific transcriptomes support a role for the stromal compartment in the spatial organization of immunity. This preserved immune zonation meets the demands for continuous protection of this vulnerable interface and suggests unique tissue-specific wiring of immunity at the human oral mucosal barrier.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146150406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-06DOI: 10.1038/s41590-026-02449-y
Jayashree Srinivasan, Colin R Moore, Aparna Calindi, Bryan R Helm, Yilin Yang, John F Moore, Hilary J Selden, Cody N Heiser, Qi Liu, Ken S Lau, Lauren I R Ehrlich
{"title":"Publisher Correction: The differentiation and function of heterogeneous thymic dendritic cell subsets require signals provided by distinct thymocyte cell types.","authors":"Jayashree Srinivasan, Colin R Moore, Aparna Calindi, Bryan R Helm, Yilin Yang, John F Moore, Hilary J Selden, Cody N Heiser, Qi Liu, Ken S Lau, Lauren I R Ehrlich","doi":"10.1038/s41590-026-02449-y","DOIUrl":"https://doi.org/10.1038/s41590-026-02449-y","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-05DOI: 10.1038/s41590-025-02412-3
Fumie Hayashi, Kristen Mittl, Ravi Dandekar, Josiah Gerdts, Ebtesam Hassan, Ryan D Schubert, Lindsay Oshiro, Rita Loudermilk, Ariele Greenfield, Danillo G Augusto, Gregory Havton, Shriya Anumarlu, Arhan Surapaneni, Akshaya Ramesh, Edwina Tran, Kanishka Koshal, Kerry Kizer, Joanna Dreux, Alaina K Cagalingan, Florian Schustek, Lena Flood, Tamson Moore, Lisa L Kirkemo, Isabelle J Fisher, Tiffany Cooper, Meagan Harms, Refujia Gomez, Claire D Clelland, Leah Sibener, Bruce A C Cree, Stephen L Hauser, Jill A Hollenbach, Marvin Gee, Michael R Wilson, Scott S Zamvil, Joseph J Sabatino
CD8+ T cells are the dominant clonally expanded lymphocyte population in multiple sclerosis (MS) lesions but their clonal identity, function and antigen specificity are not well understood. A comprehensive single-cell RNA-sequencing and T cell receptor-sequencing analysis of the cerebrospinal fluid and blood from individuals in the MS and control cohorts revealed a subset of 23 highly expanded and activated CD8+ T cell clonotypes that were enriched predominantly in the cerebrospinal fluid in the MS cohort. Using unbiased and targeted antigen discovery approaches, six CD8+ T cell clonotypes recognizing Epstein-Barr virus (EBV) antigens and multiple novel mimotopes were identified. Although the majority of mimotopes did not elicit functional responses, three of the expanded CD8+ T cell receptors from patients with MS were reactive to EBV. EBV DNA and transcripts were detected in cerebrospinal fluid, including in patients with MS who had highly expanded EBV-specific CD8+ T cells. These findings shed vital insight into the role of CD8+ T cells in MS and support an important role of EBV in MS immunopathology.
{"title":"Antigen specificity of clonally enriched CD8<sup>+</sup> T cells in multiple sclerosis.","authors":"Fumie Hayashi, Kristen Mittl, Ravi Dandekar, Josiah Gerdts, Ebtesam Hassan, Ryan D Schubert, Lindsay Oshiro, Rita Loudermilk, Ariele Greenfield, Danillo G Augusto, Gregory Havton, Shriya Anumarlu, Arhan Surapaneni, Akshaya Ramesh, Edwina Tran, Kanishka Koshal, Kerry Kizer, Joanna Dreux, Alaina K Cagalingan, Florian Schustek, Lena Flood, Tamson Moore, Lisa L Kirkemo, Isabelle J Fisher, Tiffany Cooper, Meagan Harms, Refujia Gomez, Claire D Clelland, Leah Sibener, Bruce A C Cree, Stephen L Hauser, Jill A Hollenbach, Marvin Gee, Michael R Wilson, Scott S Zamvil, Joseph J Sabatino","doi":"10.1038/s41590-025-02412-3","DOIUrl":"https://doi.org/10.1038/s41590-025-02412-3","url":null,"abstract":"<p><p>CD8<sup>+</sup> T cells are the dominant clonally expanded lymphocyte population in multiple sclerosis (MS) lesions but their clonal identity, function and antigen specificity are not well understood. A comprehensive single-cell RNA-sequencing and T cell receptor-sequencing analysis of the cerebrospinal fluid and blood from individuals in the MS and control cohorts revealed a subset of 23 highly expanded and activated CD8<sup>+</sup> T cell clonotypes that were enriched predominantly in the cerebrospinal fluid in the MS cohort. Using unbiased and targeted antigen discovery approaches, six CD8<sup>+</sup> T cell clonotypes recognizing Epstein-Barr virus (EBV) antigens and multiple novel mimotopes were identified. Although the majority of mimotopes did not elicit functional responses, three of the expanded CD8<sup>+</sup> T cell receptors from patients with MS were reactive to EBV. EBV DNA and transcripts were detected in cerebrospinal fluid, including in patients with MS who had highly expanded EBV-specific CD8<sup>+</sup> T cells. These findings shed vital insight into the role of CD8<sup>+</sup> T cells in MS and support an important role of EBV in MS immunopathology.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-05DOI: 10.1038/s41590-025-02415-0
Adelaide Gelineau, Brian D Brown, Edward J Hall, Lucy L Wang, Ronald N Germain, Christophe Benoist
{"title":"Immunological knowledge.","authors":"Adelaide Gelineau, Brian D Brown, Edward J Hall, Lucy L Wang, Ronald N Germain, Christophe Benoist","doi":"10.1038/s41590-025-02415-0","DOIUrl":"https://doi.org/10.1038/s41590-025-02415-0","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146125797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-04DOI: 10.1038/s41590-025-02414-1
Arundhoti Das, Yi Ding, Christelle Harly, Avinash Bhandoola
Innate lymphoid cells (ILCs) are a diverse group of immune cells that possess many effector functions of T cells but lack somatically generated receptors. They have crucial roles in early immune responses and in maintaining tissue integrity. We review ILC developmental pathways and progenitors in mice, with a particular focus on adult bone marrow but also addressing fetal liver. We present recent insights into the earliest steps of ILC specification, as well as new evidence for developmental pathways that generate two functionally distinct types of natural killer cells. The anatomical locations where ILC progenitors are identified are outlined and evidence supporting ILC development in tissues examined. In addition, key transcriptional regulators that support ILC development are discussed. Although ILC and T-lineage cells use many of the same transcriptional controllers during development, we present new evidence indicating ILC transcriptional programs diverge from T-lineage programs at the earliest known steps of ILC lineage specification.
{"title":"The development of innate lymphoid cells.","authors":"Arundhoti Das, Yi Ding, Christelle Harly, Avinash Bhandoola","doi":"10.1038/s41590-025-02414-1","DOIUrl":"https://doi.org/10.1038/s41590-025-02414-1","url":null,"abstract":"<p><p>Innate lymphoid cells (ILCs) are a diverse group of immune cells that possess many effector functions of T cells but lack somatically generated receptors. They have crucial roles in early immune responses and in maintaining tissue integrity. We review ILC developmental pathways and progenitors in mice, with a particular focus on adult bone marrow but also addressing fetal liver. We present recent insights into the earliest steps of ILC specification, as well as new evidence for developmental pathways that generate two functionally distinct types of natural killer cells. The anatomical locations where ILC progenitors are identified are outlined and evidence supporting ILC development in tissues examined. In addition, key transcriptional regulators that support ILC development are discussed. Although ILC and T-lineage cells use many of the same transcriptional controllers during development, we present new evidence indicating ILC transcriptional programs diverge from T-lineage programs at the earliest known steps of ILC lineage specification.</p>","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-03DOI: 10.1038/s41590-025-02409-y
Julià Blanco
{"title":"Better and closer glycan-independent anti-V3 antibodies to help HIV-1 vaccine.","authors":"Julià Blanco","doi":"10.1038/s41590-025-02409-y","DOIUrl":"https://doi.org/10.1038/s41590-025-02409-y","url":null,"abstract":"","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":" ","pages":""},"PeriodicalIF":27.6,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-03DOI: 10.1038/s41590-025-02408-z
Ignacio Relano-Rodriguez, Jianqiu Du, Zi Jie Lin, Margaret Kerwin, Marta Tarquis-Medina, Eduardo Urbano, Jiayan Cui, Meagan Watkins, Christy L. Lavine, Peng Zhao, Rumi Habib, Colby Agostino, Sukanya Ghosh, Joyce Park, Caroline Boroughs, Agnes A. Walsh, Mariane B. Melo, Niharika Shukla, George M. Shaw, Beatrice H. Hahn, Darrell J. Irvine, Lance Wells, David B. Weiner, Michael S. Seaman, Daniel W. Kulp, Ronald S. Veazey, Jesper Pallesen, Amelia Escolano
Sequential immunization is a promising approach to elicit broadly neutralizing antibodies (bNAbs) against the HIV-1 Envelope (Env). However, available protocols are inefficient and involve multiple immunizations over long periods of time. Here, we present WIN332, a new engineered Env immunogen that induces a new class of Asn332-glycan-independent antibodies to the conserved V3-glycan epitope of Env with low inhibitory activity indicative of a neutralization activity after a single bolus immunization in nonhuman primates. WIN332 binds to precursors of canonical human Asn332-glycan-dependent (type-I) V3-glycan bNAbs but also of a first-of-its-class Asn332-glycan-independent (type-II) V3-glycan bNAb. A single immunization elicits low inhibitory serum and monoclonal antibodies that are boosted and affinity matured with a heterologous immunogen. Electron microscopy polyclonal epitope mapping analysis of serum antibodies, antibody cloning and cryogenic electron microscopy analysis reveals that WIN332 elicits Asn332-glycan-independent antibodies with striking sequence and binding similarities with the most potent human type-I and type-II V3-glycan bNAbs. Thus, WIN332 is a promising vaccine candidate to streamline V3-glycan bNAb elicitation.
{"title":"Rapid elicitation of neutralizing Asn332-glycan-independent antibodies to the V3-glycan epitope of HIV-1 Env in nonhuman primates","authors":"Ignacio Relano-Rodriguez, Jianqiu Du, Zi Jie Lin, Margaret Kerwin, Marta Tarquis-Medina, Eduardo Urbano, Jiayan Cui, Meagan Watkins, Christy L. Lavine, Peng Zhao, Rumi Habib, Colby Agostino, Sukanya Ghosh, Joyce Park, Caroline Boroughs, Agnes A. Walsh, Mariane B. Melo, Niharika Shukla, George M. Shaw, Beatrice H. Hahn, Darrell J. Irvine, Lance Wells, David B. Weiner, Michael S. Seaman, Daniel W. Kulp, Ronald S. Veazey, Jesper Pallesen, Amelia Escolano","doi":"10.1038/s41590-025-02408-z","DOIUrl":"https://doi.org/10.1038/s41590-025-02408-z","url":null,"abstract":"Sequential immunization is a promising approach to elicit broadly neutralizing antibodies (bNAbs) against the HIV-1 Envelope (Env). However, available protocols are inefficient and involve multiple immunizations over long periods of time. Here, we present WIN332, a new engineered Env immunogen that induces a new class of Asn332-glycan-independent antibodies to the conserved V3-glycan epitope of Env with low inhibitory activity indicative of a neutralization activity after a single bolus immunization in nonhuman primates. WIN332 binds to precursors of canonical human Asn332-glycan-dependent (type-I) V3-glycan bNAbs but also of a first-of-its-class Asn332-glycan-independent (type-II) V3-glycan bNAb. A single immunization elicits low inhibitory serum and monoclonal antibodies that are boosted and affinity matured with a heterologous immunogen. Electron microscopy polyclonal epitope mapping analysis of serum antibodies, antibody cloning and cryogenic electron microscopy analysis reveals that WIN332 elicits Asn332-glycan-independent antibodies with striking sequence and binding similarities with the most potent human type-I and type-II V3-glycan bNAbs. Thus, WIN332 is a promising vaccine candidate to streamline V3-glycan bNAb elicitation.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"61 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-02-03DOI: 10.1038/s41590-025-02385-3
Lutz Gieselmann, Andrew T. DeLaitsch, Malena Rohde, Caelan Radford, Johanna Worczinski, Anna Ashurov, Elvin Ahmadov, Judith A. Burger, Colin Havenar-Daughton, Sharvari Deshpande, Federico Giovannoni, Davide Corti, Christoph Kreer, Meryem Seda Ercanoglu, Philipp Schommers, Ivelin S. Georgiev, Anthony P. West Jr., Jacqueline Knüfer, Ricarda Stumpf, Arne Kroidl, Christof Geldmacher, Lucas Maganga, Wiston William, Nyanda E. Ntinginya, Michael Hoelscher, Zhengrong Yang, Qing Wei, Matthew B. Renfrow, Todd J. Green, Jan Novak, Marit J. van Gils, Harry B. Gristick, Henning Gruell, Jesse D. Bloom, Michael S. Seaman, Pamela J. Bjorkman, Florian Klein
Broadly neutralizing antibodies (bNAbs) against HIV-1 can suppress viremia in vivo and inform vaccine development. Here we characterized 007, a V3 glycan site bNAb exhibiting high levels of antiviral activity against multiclade pseudovirus panels. 007 targets an N332gp120 glycan-independent V3 epitope, a site of the HIV-1 envelope protein (Env) vulnerability to which only weakly neutralizing antibodies had previously been identified. Functional analyses demonstrated distinct binding and neutralization profiles compared to classical V3 glycan site bNAbs. A 007 Fab-Env cryogenic electron microscopy structure revealed contacts with the V3 324GD/NIR327 motif and interactions with N156gp120 and N301gp120 glycans. In contrast to classical V3 bNAbs, 007 binding to Env does not depend on the N332gp120 glycan, rendering it resistant to common escape mutations. Structures of 007 IgG-Env trimer complexes showed two Env trimers crosslinked by three bivalent IgGs. Bivalent 007 IgG was more potent than monovalent 007 IgG heterodimer, suggesting a role for avidity in potent neutralization. Finally, in HIV-1ADA-infected humanized mice, 007 caused transient decline of viremia and overcame classical V3 escape mutations, highlighting 007’s potential for HIV-1 prevention, therapy, functional cure and vaccine design.
{"title":"Identification of a potent V3 glycan site broadly neutralizing antibody targeting an N332gp120 glycan-independent epitope","authors":"Lutz Gieselmann, Andrew T. DeLaitsch, Malena Rohde, Caelan Radford, Johanna Worczinski, Anna Ashurov, Elvin Ahmadov, Judith A. Burger, Colin Havenar-Daughton, Sharvari Deshpande, Federico Giovannoni, Davide Corti, Christoph Kreer, Meryem Seda Ercanoglu, Philipp Schommers, Ivelin S. Georgiev, Anthony P. West Jr., Jacqueline Knüfer, Ricarda Stumpf, Arne Kroidl, Christof Geldmacher, Lucas Maganga, Wiston William, Nyanda E. Ntinginya, Michael Hoelscher, Zhengrong Yang, Qing Wei, Matthew B. Renfrow, Todd J. Green, Jan Novak, Marit J. van Gils, Harry B. Gristick, Henning Gruell, Jesse D. Bloom, Michael S. Seaman, Pamela J. Bjorkman, Florian Klein","doi":"10.1038/s41590-025-02385-3","DOIUrl":"https://doi.org/10.1038/s41590-025-02385-3","url":null,"abstract":"Broadly neutralizing antibodies (bNAbs) against HIV-1 can suppress viremia in vivo and inform vaccine development. Here we characterized 007, a V3 glycan site bNAb exhibiting high levels of antiviral activity against multiclade pseudovirus panels. 007 targets an N332gp120 glycan-independent V3 epitope, a site of the HIV-1 envelope protein (Env) vulnerability to which only weakly neutralizing antibodies had previously been identified. Functional analyses demonstrated distinct binding and neutralization profiles compared to classical V3 glycan site bNAbs. A 007 Fab-Env cryogenic electron microscopy structure revealed contacts with the V3 324GD/NIR327 motif and interactions with N156gp120 and N301gp120 glycans. In contrast to classical V3 bNAbs, 007 binding to Env does not depend on the N332gp120 glycan, rendering it resistant to common escape mutations. Structures of 007 IgG-Env trimer complexes showed two Env trimers crosslinked by three bivalent IgGs. Bivalent 007 IgG was more potent than monovalent 007 IgG heterodimer, suggesting a role for avidity in potent neutralization. Finally, in HIV-1ADA-infected humanized mice, 007 caused transient decline of viremia and overcame classical V3 escape mutations, highlighting 007’s potential for HIV-1 prevention, therapy, functional cure and vaccine design.","PeriodicalId":19032,"journal":{"name":"Nature Immunology","volume":"59 1","pages":""},"PeriodicalIF":30.5,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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