Co-evolution of a broadly neutralizing HIV-1 antibody and founder virus
Hua-Xin Liao,Rebecca M. Lynch,Tongqing Zhou,Feng Gao,Feng Gao,S. Munir Alam,S. Munir Alam,Scott D. Boyd,Andrew Fire,Krishna M. Roskin,Chaim A. Schramm,Zhenhai Zhang,Jiang Zhu,Lawrence Shapiro,Lawrence Shapiro,Nisc Comparative Sequencing Program,James C. Mullikin,Sandrasegaram Gnanakaran,Peter T. Hraber,Kevin Wiehe,Kevin Wiehe,Garnett Kelsoe,Garnett Kelsoe,Guang Yang,Guang Yang,Shi-Mao Xia,Shi-Mao Xia,David C. Montefiori,David C. Montefiori,Robert Parks,Robert Parks,Krissey E. Lloyd,Krissey E. Lloyd,Richard M. Scearce,Richard M. Scearce,Kelly A. Soderberg,Kelly A. Soderberg,Myron S. Cohen,Gift Kamanga,Mark K. Louder,Lillian Tran,Yue Chen,Yue Chen,Fangping Cai,Fangping Cai,Sheri Chen,Sheri Chen,Stephanie Moquin,Xiulian Du,M. Gordon Joyce,Sanjay Srivatsan,Baoshan Zhang,Anqi Zheng,George M. Shaw,Beatrice H. Hahn,Thomas B. Kepler,Bette T. Korber,Peter D. Kwong,John R. Mascola,Barton F. Haynes,Barton F. Haynes +60 more
TLDR
The isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection and its co-crystal structure revealed a new loop-based mechanism of CD4-binding-site recognition.Abstract:
Current human immunodeficiency virus-1 (HIV-1) vaccines elicit strain-specific neutralizing antibodies. However, cross-reactive neutralizing antibodies arise in approximately 20% of HIV-1-infected individuals, and details of their generation could provide a blueprint for effective vaccination. Here we report the isolation, evolution and structure of a broadly neutralizing antibody from an African donor followed from the time of infection. The mature antibody, CH103, neutralized approximately 55% of HIV-1 isolates, and its co-crystal structure with the HIV-1 envelope protein gp120 revealed a new loop-based mechanism of CD4-binding-site recognition. Virus and antibody gene sequencing revealed concomitant virus evolution and antibody maturation. Notably, the unmutated common ancestor of the CH103 lineage avidly bound the transmitted/founder HIV-1 envelope glycoprotein, and evolution of antibody neutralization breadth was preceded by extensive viral diversification in and near the CH103 epitope. These data determine the viral and antibody evolution leading to induction of a lineage of HIV-1 broadly neutralizing antibodies, and provide insights into strategies to elicit similar antibodies by vaccination.read more
Citations
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Human neutralizing antibodies elicited by SARS-CoV-2 infection.
Bin Ju,Qi Zhang,Jiwan Ge,Ruoke Wang,Jing Sun,Xiangyang Ge,Jiazhen Yu,Sisi Shan,Bing Zhou,Shuo Song,Xian Tang,Jinfang Yu,Jun Lan,Jing Yuan,Haiyan Wang,Juanjuan Zhao,Shuye Zhang,Youchun Wang,Xuanling Shi,Lei Liu,Jincun Zhao,Xinquan Wang,Zheng Zhang,Linqi Zhang +23 more
TL;DR: In a study of antibodies isolated from patients infected with SARS-CoV-2, antibodies that potently neutralized the virus competed with angiotensin-converting enzyme 2 for binding to the receptor-binding domain of the viral spike protein, suggesting that antibodies that disrupt this interaction could be developed to treat Sars-Cov-2 infection.
Journal ArticleDOI
Human Circulating PD-1+CXCR3−CXCR5+ Memory Tfh Cells Are Highly Functional and Correlate with Broadly Neutralizing HIV Antibody Responses
Michela Locci,Michela Locci,Colin Havenar-Daughton,Colin Havenar-Daughton,Elise Landais,Jennifer E. Wu,Mark A. Kroenke,Cecilia S. Lindestam Arlehamn,Laura F. Su,Rafael Cubas,Mark M. Davis,Alessandro Sette,Elias K. Haddad,Pascal Poignard,Pascal Poignard,Shane Crotty,Shane Crotty +16 more
TL;DR: In normal individuals a subpopulation of circulating memory PD-1⁺CXCR5⁺CD4⁺ T cells that are resting memory cells most related to bona fide GC Tfh cells are identified that correlated with the development of bnAbs against HIV in a large cohort of HIV⁺ individuals.
Journal ArticleDOI
Cryo-EM Structure of a Fully Glycosylated Soluble Cleaved HIV-1 Envelope Trimer
Dmitry Lyumkis,Jean-Philippe Julien,Natalia de Val,Albert Cupo,Clinton S. Potter,Per Johan Klasse,Dennis R. Burton,Rogier W. Sanders,Rogier W. Sanders,John P. Moore,Bridget Carragher,Ian A. Wilson,Andrew B. Ward,Andrew B. Ward +13 more
TL;DR: A cryo–electron microscopy reconstruction and structural model of a cleaved, soluble Env trimer in complex with a CD4 binding site bnAb, PGV04 is presented, which reveals the spatial arrangement of Env components, including the V1/V2, V3, HR1, and HR2 domains, as well as shielding glycans.
Journal ArticleDOI
Structure and immune recognition of trimeric pre-fusion HIV-1 Env
Marie Pancera,Tongqing Zhou,Aliaksandr Druz,Ivelin S. Georgiev,Cinque Soto,Jason Gorman,Jinghe Huang,Priyamvada Acharya,Gwo-Yu Chuang,Gilad Ofek,Guillaume Stewart-Jones,Jonathan Stuckey,Robert T. Bailer,M. Gordon Joyce,Mark K. Louder,Nancy Tumba,Yongping Yang,Baoshan Zhang,Myron S. Cohen,Barton F. Haynes,John R. Mascola,Lynn Morris,James B. Munro,Scott C. Blanchard,Walther Mothes,Mark Connors,Peter D. Kwong +26 more
TL;DR: The structure at 3.5 Å resolution for an HIV-1 Env trimer captured in a mature closed state by antibodies PGT122 and 35O22 is reported, revealing the pre-fusion conformation of gp41, rearrangements needed for fusion activation, and defines parameters of immune evasion and immune recognition.
Journal ArticleDOI
HIV infection: epidemiology, pathogenesis, treatment, and prevention
TL;DR: The role of immune activation in the pathogenesis of non-AIDS clinical events (major causes of morbidity and mortality in people on antiretroviral therapy) is receiving increased recognition and breakthroughs in the prevention of HIV important to public health include male medical circumcision.
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