Joana Dias, Giulia Fabozzi, Slim Fourati, Xuejun Chen, Cuiping Liu, David R. Ambrozak, Amy Ransier, Farida Laboune, Jianfei Hu, Wei Shi, Kylie March, Anna A. Maximova, Stephen D. Schmidt, Jakob Samsel, Chloe A. Talana, Keenan Ernste, Sung Hee Ko, Margaret E. Lucas, Pierce E. Radecki, Kristin L. Boswell, Yoshiaki Nishimura, John-Paul Todd, Malcolm A. Martin, Constantinos Petrovas, Eli A. Boritz, Nicole A. Doria-Rose, Daniel C. Douek, Rafick-Pierre Sékaly, Jeffrey D. Lifson, Mangaiarkarasi Asokan, Lucio Gama, John R. Mascola, Amarendra Pegu, Richard A. Koup
{"title":"Administration of anti-HIV-1 broadly neutralizing monoclonal antibodies with increased affinity to Fcγ receptors during acute SHIVAD8-EO infection","authors":"Joana Dias, Giulia Fabozzi, Slim Fourati, Xuejun Chen, Cuiping Liu, David R. Ambrozak, Amy Ransier, Farida Laboune, Jianfei Hu, Wei Shi, Kylie March, Anna A. Maximova, Stephen D. Schmidt, Jakob Samsel, Chloe A. Talana, Keenan Ernste, Sung Hee Ko, Margaret E. Lucas, Pierce E. Radecki, Kristin L. Boswell, Yoshiaki Nishimura, John-Paul Todd, Malcolm A. Martin, Constantinos Petrovas, Eli A. Boritz, Nicole A. Doria-Rose, Daniel C. Douek, Rafick-Pierre Sékaly, Jeffrey D. Lifson, Mangaiarkarasi Asokan, Lucio Gama, John R. Mascola, Amarendra Pegu, Richard A. Koup","doi":"10.1038/s41467-024-51848-y","DOIUrl":null,"url":null,"abstract":"<p>Anti-HIV-1 broadly neutralizing antibodies (bNAbs) have the dual potential of mediating virus neutralization and antiviral effector functions through their Fab and Fc domains, respectively. So far, bNAbs with enhanced Fc effector functions in vitro have only been tested in NHPs during chronic simian-HIV (SHIV) infection. Here, we investigate the effects of administering in acute SHIV<sub>AD8-EO</sub> infection either wild-type (WT) bNAbs or bNAbs carrying the S239D/I332E/A330L (DEL) mutation, which increases binding to FcγRs. Emergence of virus in plasma and lymph nodes (LNs) was delayed by bNAb treatment and occurred earlier in monkeys given DEL bNAbs than in those given WT bNAbs, consistent with faster clearance of DEL bNAbs from plasma. DEL bNAb-treated monkeys had higher levels of circulating virus-specific IFNγ single-producing CD8<sup>+</sup> CD69<sup>+</sup> T cells than the other groups. In LNs, WT bNAbs were evenly distributed between follicular and extrafollicular areas, but DEL bNAbs predominated in the latter. At week 8 post-challenge, LN monocytes and NK cells from DEL bNAb-treated monkeys upregulated proinflammatory signaling pathways and LN T cells downregulated TNF signaling via NF-κB. Overall, bNAbs with increased affinity to FcγRs shape innate and adaptive cellular immunity, which may be important to consider in future strategies of passive bNAb therapy.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":null,"pages":null},"PeriodicalIF":14.7000,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-024-51848-y","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
Abstract
Anti-HIV-1 broadly neutralizing antibodies (bNAbs) have the dual potential of mediating virus neutralization and antiviral effector functions through their Fab and Fc domains, respectively. So far, bNAbs with enhanced Fc effector functions in vitro have only been tested in NHPs during chronic simian-HIV (SHIV) infection. Here, we investigate the effects of administering in acute SHIVAD8-EO infection either wild-type (WT) bNAbs or bNAbs carrying the S239D/I332E/A330L (DEL) mutation, which increases binding to FcγRs. Emergence of virus in plasma and lymph nodes (LNs) was delayed by bNAb treatment and occurred earlier in monkeys given DEL bNAbs than in those given WT bNAbs, consistent with faster clearance of DEL bNAbs from plasma. DEL bNAb-treated monkeys had higher levels of circulating virus-specific IFNγ single-producing CD8+ CD69+ T cells than the other groups. In LNs, WT bNAbs were evenly distributed between follicular and extrafollicular areas, but DEL bNAbs predominated in the latter. At week 8 post-challenge, LN monocytes and NK cells from DEL bNAb-treated monkeys upregulated proinflammatory signaling pathways and LN T cells downregulated TNF signaling via NF-κB. Overall, bNAbs with increased affinity to FcγRs shape innate and adaptive cellular immunity, which may be important to consider in future strategies of passive bNAb therapy.
期刊介绍:
Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.