@article{5deee71d307a4156951fc77588384519,
title = "Particulate Array of Well-Ordered HIV Clade C Env Trimers Elicits Neutralizing Antibodies that Display a Unique V2 Cap Approach",
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.",
keywords = "B cell responses, HIV-1, clade C, envelope glycoproteins, epitope, germinal centers, liposome, monoclonal antibody, trimers, vaccine",
author = "Paola Martinez-Murillo and Karen Tran and Javier Guenaga and Gustaf Lindgren and Monika {\`A}dori and Yu Feng and Phad, {Ganesh E.} and {V{\'a}zquez Bernat}, N{\'e}stor and Shridhar Bale and Jidnyasa Ingale and Viktoriya Dubrovskaya and Sijy O'Dell and Lotta Pramanik and Mats Sp{\aa}ngberg and Martin Corcoran and Karin Lor{\'e} and Mascola, {John R.} and Wyatt, {Richard T.} and {Karlsson Hedestam}, {Gunilla B.}",
note = "Funding Information: We thank Bengt Eriksson and all personnel at Astrid Fagraeus laboratory for expert assistance with rhesus macaques and Richard Wilson and Barbara Lemaire for assistance with protein production. We also thank Novavax, AB, for making the Matrix-M adjuvant available and Christina Corbaci for help with the graphical abstract. EM analysis of the trimer-conjugated liposomes was performed at the TSRI Microscopy Core with assistance from Malcom Wood and Theresa Fassel. EM imaging of Fab:trimer complexes and 3D reconstructions were performed by NanoImaging Services. This work was funded by an NIH P01 grant AI104722 (HIVRAD), the intramural research program of the Vaccine Research Center, NIAID, NIH, the Scripps CHAVI-ID grant AI100663 (R.T.W.), grants for doctoral education to P.M.-M., G.L., and G.E.P., and from the IAVI Neutralizing Antibody Consortium (R.T.W. and G.K.H.) and its generous donors, including the Bill and Melinda Gates Foundation CAVD and USAID. The full list of IAVI donors can be found at www.iavi.org. Publisher Copyright: {\textcopyright} 2017 Elsevier Inc.",
year = "2017",
month = may,
day = "16",
doi = "10.1016/j.immuni.2017.04.021",
language = "English (US)",
volume = "46",
pages = "804--817.e7",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "5",
}