Hua Wang, Cheng Cheng, James L. Dal Santo, Chen-Hsiang Shen, Tatsiana Bylund, Amy R. Henry, Colin A. Howe, Juyun Hwang, Nicholas C. Morano, Daniel J. Morris, Sergei Pletnev, Ryan S. Roark, Tongqing Zhou, Bryan T. Hansen, Forrest H. Hoyt, Timothy S. Johnston, Shuyi Wang, Baoshan Zhang, David R. Ambrozak, Jordan E. Becker, Peter D. Kwong
{"title":"在以融合肽为前体的 SHIV 感染猕猴体内发挥强效、广泛的 HIV-1 中和作用","authors":"Hua Wang, Cheng Cheng, James L. Dal Santo, Chen-Hsiang Shen, Tatsiana Bylund, Amy R. Henry, Colin A. Howe, Juyun Hwang, Nicholas C. Morano, Daniel J. Morris, Sergei Pletnev, Ryan S. Roark, Tongqing Zhou, Bryan T. Hansen, Forrest H. Hoyt, Timothy S. Johnston, Shuyi Wang, Baoshan Zhang, David R. Ambrozak, Jordan E. Becker, Peter D. Kwong","doi":"10.1016/j.cell.2024.10.003","DOIUrl":null,"url":null,"abstract":"An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%–77% breadth (geometric mean 50% inhibitory dilution [ID<sub>50</sub>] ∼100) on a 208-strain panel. Molecular dissection of these responses by antibody isolation and cryo-electron microscopy (cryo-EM) structure determination revealed 15 of 16 antibody lineages with cross-clade neutralization to be directed toward the fusion-peptide site of vulnerability. In each macaque, isolated antibodies from memory B cells recapitulated the plasma-neutralizing response, with fusion-peptide-binding antibodies reaching breadths of 40%–60% (50% inhibitory concentration [IC<sub>50</sub>] < 50 μg/mL) and total lineage-concentrations estimates of 50–200 μg/mL. Longitudinal mapping indicated that these responses arose prior to SHIV infection. Collectively, these results provide <em>in vivo</em> molecular examples for one to a few B cell lineages affording potent, broadly neutralizing plasma responses.","PeriodicalId":9656,"journal":{"name":"Cell","volume":null,"pages":null},"PeriodicalIF":45.5000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques\",\"authors\":\"Hua Wang, Cheng Cheng, James L. Dal Santo, Chen-Hsiang Shen, Tatsiana Bylund, Amy R. Henry, Colin A. Howe, Juyun Hwang, Nicholas C. Morano, Daniel J. Morris, Sergei Pletnev, Ryan S. Roark, Tongqing Zhou, Bryan T. Hansen, Forrest H. Hoyt, Timothy S. Johnston, Shuyi Wang, Baoshan Zhang, David R. Ambrozak, Jordan E. Becker, Peter D. Kwong\",\"doi\":\"10.1016/j.cell.2024.10.003\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%–77% breadth (geometric mean 50% inhibitory dilution [ID<sub>50</sub>] ∼100) on a 208-strain panel. Molecular dissection of these responses by antibody isolation and cryo-electron microscopy (cryo-EM) structure determination revealed 15 of 16 antibody lineages with cross-clade neutralization to be directed toward the fusion-peptide site of vulnerability. In each macaque, isolated antibodies from memory B cells recapitulated the plasma-neutralizing response, with fusion-peptide-binding antibodies reaching breadths of 40%–60% (50% inhibitory concentration [IC<sub>50</sub>] < 50 μg/mL) and total lineage-concentrations estimates of 50–200 μg/mL. Longitudinal mapping indicated that these responses arose prior to SHIV infection. Collectively, these results provide <em>in vivo</em> molecular examples for one to a few B cell lineages affording potent, broadly neutralizing plasma responses.\",\"PeriodicalId\":9656,\"journal\":{\"name\":\"Cell\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":45.5000,\"publicationDate\":\"2024-10-28\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1016/j.cell.2024.10.003\",\"RegionNum\":1,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.cell.2024.10.003","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Potent and broad HIV-1 neutralization in fusion peptide-primed SHIV-infected macaques
An antibody-based HIV-1 vaccine will require the induction of potent cross-reactive HIV-1-neutralizing responses. To demonstrate feasibility toward this goal, we combined vaccination targeting the fusion-peptide site of vulnerability with infection by simian-human immunodeficiency virus (SHIV). In four macaques with vaccine-induced neutralizing responses, SHIV infection boosted plasma neutralization to 45%–77% breadth (geometric mean 50% inhibitory dilution [ID50] ∼100) on a 208-strain panel. Molecular dissection of these responses by antibody isolation and cryo-electron microscopy (cryo-EM) structure determination revealed 15 of 16 antibody lineages with cross-clade neutralization to be directed toward the fusion-peptide site of vulnerability. In each macaque, isolated antibodies from memory B cells recapitulated the plasma-neutralizing response, with fusion-peptide-binding antibodies reaching breadths of 40%–60% (50% inhibitory concentration [IC50] < 50 μg/mL) and total lineage-concentrations estimates of 50–200 μg/mL. Longitudinal mapping indicated that these responses arose prior to SHIV infection. Collectively, these results provide in vivo molecular examples for one to a few B cell lineages affording potent, broadly neutralizing plasma responses.
期刊介绍:
Cells is an international, peer-reviewed, open access journal that focuses on cell biology, molecular biology, and biophysics. It is affiliated with several societies, including the Spanish Society for Biochemistry and Molecular Biology (SEBBM), Nordic Autophagy Society (NAS), Spanish Society of Hematology and Hemotherapy (SEHH), and Society for Regenerative Medicine (Russian Federation) (RPO).
The journal publishes research findings of significant importance in various areas of experimental biology, such as cell biology, molecular biology, neuroscience, immunology, virology, microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. The primary criterion for considering papers is whether the results contribute to significant conceptual advances or raise thought-provoking questions and hypotheses related to interesting and important biological inquiries.
In addition to primary research articles presented in four formats, Cells also features review and opinion articles in its "leading edge" section, discussing recent research advancements and topics of interest to its wide readership.