Paola Martinez-Murillo1, Karen Tran2, Javier Guenaga2, Gustaf Lindgren3, Monika Àdori1, Yu Feng2, Ganesh E Phad1, Néstor Vázquez Bernat1, Shridhar Bale2, Jidnyasa Ingale2, Viktoriya Dubrovskaya2, Sijy O'Dell4, Lotta Pramanik1, Mats Spångberg5, Martin Corcoran1, Karin Loré3, John R Mascola4, Richard T Wyatt6, Gunilla B Karlsson Hedestam7. 1. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden. 2. IAVI Neutralizing Antibody Center, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. 3. Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, 171 77 Solna, Sweden. 4. Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. 5. Astrid Fagraeus Laboratory, Comparative Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden. 6. IAVI Neutralizing Antibody Center, Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA. Electronic address: wyatt@scripps.edu. 7. Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden. Electronic address: gunilla.karlsson.hedestam@ki.se.
Abstract
The development of soluble envelope glycoprotein (Env) mimetics displaying ordered trimeric symmetry has ushered in a new era in HIV-1 vaccination. The recently reported native, flexibly linked (NFL) design allows the generation of native-like trimers from clinical isolates at high yields and homogeneity. As the majority of infections world-wide are of the clade C subtype, we examined responses in non-human primates to well-ordered subtype C 16055 trimers administered in soluble or high-density liposomal formats. We detected superior germinal center formation and enhanced autologous neutralizing antibodies against the neutralization-resistant (tier 2) 16055 virus following inoculation of liposome-arrayed trimers. Epitope mapping of the neutralizing monoclonal antibodies (mAbs) indicated major contacts with the V2 apex, and 3D electron microscopy reconstructions of Fab-trimer complexes revealed a horizontal binding angle to the Env spike. These vaccine-elicited mAbs target the V2 cap, demonstrating a means to accomplish tier 2 virus neutralization by penetrating the dense N-glycan shield.
The development of soluble envelope glycoprotein (n class="Gene">Env) mimetics displaying ordered trimeric symmetry has ushered in a new era in HIV-1 vaccination. The recently reported native, flexibly linked (NFL) design allows the generation of native-like trimers from clinical isolates at high yields and homogeneity. As the majority of infections world-wide are of the clade C subtype, we examined responses in non-human primates to well-ordered subtype C 16055 trimers administered in soluble or high-density liposomal formats. We detected superior germinal center formation and enhanced autologous neutralizing antibodies against the neutralization-resistant (tier 2) 16055 virus following inoculation of liposome-arrayed trimers. Epitope mapping of the neutralizing monoclonal antibodies (mAbs) indicated major contacts with the V2 apex, and 3D electron microscopy reconstructions of Fab-trimer complexes revealed a horizontal binding angle to the Env spike. These vaccine-elicited mAbs target the V2 cap, demonstrating a means to accomplish tier 2 virus neutralization by penetrating the dense N-glycan shield.
Authors: M P Lefranc; V Giudicelli; C Ginestoux; J Bodmer; W Müller; R Bontrop; M Lemaitre; A Malik; V Barbié; D Chaume Journal: Nucleic Acids Res Date: 1999-01-01 Impact factor: 16.971
Authors: Christopher Sundling; Yuxing Li; Nick Huynh; Christian Poulsen; Richard Wilson; Sijy O'Dell; Yu Feng; John R Mascola; Richard T Wyatt; Gunilla B Karlsson Hedestam Journal: Sci Transl Med Date: 2012-07-11 Impact factor: 17.956
Authors: Xiping Wei; Julie M Decker; Shuyi Wang; Huxiong Hui; John C Kappes; Xiaoyun Wu; Jesus F Salazar-Gonzalez; Maria G Salazar; J Michael Kilby; Michael S Saag; Natalia L Komarova; Martin A Nowak; Beatrice H Hahn; Peter D Kwong; George M Shaw Journal: Nature Date: 2003-03-20 Impact factor: 49.962
Authors: Hua-Xin Liao; Mattia Bonsignori; S Munir Alam; Jason S McLellan; Georgia D Tomaras; M Anthony Moody; Daniel M Kozink; Kwan-Ki Hwang; Xi Chen; Chun-Yen Tsao; Pinghuang Liu; Xiaozhi Lu; Robert J Parks; David C Montefiori; Guido Ferrari; Justin Pollara; Mangala Rao; Kristina K Peachman; Sampa Santra; Norman L Letvin; Nicos Karasavvas; Zhi-Yong Yang; Kaifan Dai; Marie Pancera; Jason Gorman; Kevin Wiehe; Nathan I Nicely; Supachai Rerks-Ngarm; Sorachai Nitayaphan; Jaranit Kaewkungwal; Punnee Pitisuttithum; James Tartaglia; Faruk Sinangil; Jerome H Kim; Nelson L Michael; Thomas B Kepler; Peter D Kwong; John R Mascola; Gary J Nabel; Abraham Pinter; Susan Zolla-Pazner; Barton F Haynes Journal: Immunity Date: 2013-01-11 Impact factor: 31.745
Authors: Nicole A Doria-Rose; Chaim A Schramm; Jason Gorman; Penny L Moore; Jinal N Bhiman; Brandon J DeKosky; Michael J Ernandes; Ivelin S Georgiev; Helen J Kim; Marie Pancera; Ryan P Staupe; Han R Altae-Tran; Robert T Bailer; Ema T Crooks; Albert Cupo; Aliaksandr Druz; Nigel J Garrett; Kam H Hoi; Rui Kong; Mark K Louder; Nancy S Longo; Krisha McKee; Molati Nonyane; Sijy O'Dell; Ryan S Roark; Rebecca S Rudicell; Stephen D Schmidt; Daniel J Sheward; Cinque Soto; Constantinos Kurt Wibmer; Yongping Yang; Zhenhai Zhang; James C Mullikin; James M Binley; Rogier W Sanders; Ian A Wilson; John P Moore; Andrew B Ward; George Georgiou; Carolyn Williamson; Salim S Abdool Karim; Lynn Morris; Peter D Kwong; Lawrence Shapiro; John R Mascola Journal: Nature Date: 2014-03-02 Impact factor: 49.962
Authors: Laura K Pritchard; Daniel I R Spencer; Louise Royle; Camille Bonomelli; Gemma E Seabright; Anna-Janina Behrens; Daniel W Kulp; Sergey Menis; Stefanie A Krumm; D Cameron Dunlop; Daniel J Crispin; Thomas A Bowden; Christopher N Scanlan; Andrew B Ward; William R Schief; Katie J Doores; Max Crispin Journal: Nat Commun Date: 2015-06-24 Impact factor: 14.919
Authors: Sergey Lyskov; Fang-Chieh Chou; Shane Ó Conchúir; Bryan S Der; Kevin Drew; Daisuke Kuroda; Jianqing Xu; Brian D Weitzner; P Douglas Renfrew; Parin Sripakdeevong; Benjamin Borgo; James J Havranek; Brian Kuhlman; Tanja Kortemme; Richard Bonneau; Jeffrey J Gray; Rhiju Das Journal: PLoS One Date: 2013-05-22 Impact factor: 3.240
Authors: Rogier W Sanders; Ronald Derking; Albert Cupo; Jean-Philippe Julien; Anila Yasmeen; Natalia de Val; Helen J Kim; Claudia Blattner; Alba Torrents de la Peña; Jacob Korzun; Michael Golabek; Kevin de Los Reyes; Thomas J Ketas; Marit J van Gils; C Richter King; Ian A Wilson; Andrew B Ward; P J Klasse; John P Moore Journal: PLoS Pathog Date: 2013-09-19 Impact factor: 6.823
Authors: Marjon Navis; Karen Tran; Shridhar Bale; Ganesh E Phad; Javier Guenaga; Richard Wilson; Martina Soldemo; Krisha McKee; Christopher Sundling; John Mascola; Yuxing Li; Richard T Wyatt; Gunilla B Karlsson Hedestam Journal: PLoS Pathog Date: 2014-08-28 Impact factor: 6.823
Authors: Yimeng Wang; Sijy O'Dell; Hannah L Turner; Chi-I Chiang; Lin Lei; Javier Guenaga; Richard Wilson; Paola Martinez-Murillo; Nicole Doria-Rose; Andrew B Ward; John R Mascola; Richard T Wyatt; Gunilla B Karlsson Hedestam; Yuxing Li Journal: J Virol Date: 2017-10-13 Impact factor: 5.103
Authors: Sebastian Ols; Lifei Yang; Elizabeth A Thompson; Pradeepa Pushparaj; Karen Tran; Frank Liang; Ang Lin; Bengt Eriksson; Gunilla B Karlsson Hedestam; Richard T Wyatt; Karin Loré Journal: Cell Rep Date: 2020-03-24 Impact factor: 9.423
Authors: Kevin O Saunders; Kevin Wiehe; Ming Tian; Priyamvada Acharya; Todd Bradley; S Munir Alam; Eden P Go; Richard Scearce; Laura Sutherland; Rory Henderson; Allen L Hsu; Mario J Borgnia; Haiyan Chen; Xiaozhi Lu; Nelson R Wu; Brian Watts; Chuancang Jiang; David Easterhoff; Hwei-Ling Cheng; Kelly McGovern; Peyton Waddicor; Aimee Chapdelaine-Williams; Amanda Eaton; Jinsong Zhang; Wes Rountree; Laurent Verkoczy; Mark Tomai; Mark G Lewis; Heather R Desaire; Robert J Edwards; Derek W Cain; Mattia Bonsignori; David Montefiori; Frederick W Alt; Barton F Haynes Journal: Science Date: 2019-12-06 Impact factor: 47.728
Authors: Talar Tokatlian; Benjamin J Read; Christopher A Jones; Daniel W Kulp; Sergey Menis; Jason Y H Chang; Jon M Steichen; Sudha Kumari; Joel D Allen; Eric L Dane; Alessia Liguori; Maya Sangesland; Daniel Lingwood; Max Crispin; William R Schief; Darrell J Irvine Journal: Science Date: 2018-12-20 Impact factor: 47.728
Authors: Reda Rawi; Lucy Rutten; Yen-Ting Lai; Adam S Olia; Sven Blokland; Jarek Juraszek; Chen-Hsiang Shen; Yaroslav Tsybovsky; Raffaello Verardi; Yongping Yang; Baoshan Zhang; Tongqing Zhou; Gwo-Yu Chuang; Peter D Kwong; Johannes P M Langedijk Journal: Cell Rep Date: 2020-11-24 Impact factor: 9.423
Authors: Sonu Kumar; Xiaohe Lin; Timothy Ngo; Benjamin Shapero; Cindy Sou; Joel D Allen; Jeffrey Copps; Lei Zhang; Gabriel Ozorowski; Linling He; Max Crispin; Andrew B Ward; Ian A Wilson; Jiang Zhu Journal: mBio Date: 2021-06-22 Impact factor: 7.867
Authors: David Peterhoff; Stefanie Thalhauser; Jan M Sobczak; Mona O Mohsen; Christoph Voigt; Nicole Seifert; Patrick Neckermann; Alexandra Hauser; Song Ding; Quentin Sattentau; Martin F Bachmann; Miriam Breunig; Ralf Wagner Journal: Vaccines (Basel) Date: 2021-06-11
Authors: Alireza Hassani Najafabadi; Zeynab Izadi Najaf Abadi; Marisa E Aikins; Kathryn E Foulds; Mitzi M Donaldson; Wenmin Yuan; Emeka B Okeke; Jutaek Nam; Yao Xu; Priyan Weerappuli; Taryn Hetrick; David Adams; Patrick A Lester; Andres M Salazar; Dan H Barouch; Anna Schwendeman; Robert A Seder; James J Moon Journal: J Control Release Date: 2021-07-16 Impact factor: 11.467