Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1

Xu, Kai; Acharya, Priyamvada; Kong, Rui; Cheng, Cheng; Chuang, Gwo-Yu; Liu, Kevin; Louder, Mark K.; O’Dell, Sijy; Rawi, Reda; Sastry, Mallika; Shen, Chen-Hsiang; Zhang, Baoshan; Zhou, Tongqing; Asokan, Mangaiarkarasi; Bailer, Robert T.; Chambers, Michael; Chen, Xuejun; Choi, Chang W.; Dandey, Venkata P.; Doria-Rose, Nicole A.; Druz, Aliaksandr; Eng, Edward T.; Farney, S. Katie; Foulds, Kathryn E.; Geng, Hui; Georgiev, Ivelin S.; Gorman, Jason; Hill, Kurt R.; Jafari, Alexander J.; Kwon, Young D.; Lai, Yen-Ting; Lemmin, Thomas; McKee, Krisha; Ohr, Tiffany Y.; Ou, Li; Peng, Dongjun; Rowshan, Ariana P.; Sheng, Zizhang; Todd, John-Paul; Tsybovsky, Yaroslav; Viox, Elise G.; Wang, Yiran; Wei, Hui; Yang, Yongping; Zhou, Amy F.; Chen, Rui; Yang, Lu; Scorpio, Diana G.; McDermott, Adrian B.; Shapiro, Lawrence; Carragher, Bridget; Potter, Clinton S.; Mascola, John R.; Kwong, Peter D.

doi:10.1038/s41591-018-0042-6

Title: Epitope-based vaccine design yields fusion peptide-directed antibodies that neutralize diverse strains of HIV-1

Journal Article · Mon Jun 04 00:00:00 EDT 2018 · Nature Medicine

DOI:https://doi.org/10.1038/s41591-018-0042-6· OSTI ID:1467705

Xu, Kai ^[1]; Acharya, Priyamvada ^[2]; Kong, Rui ^[1]; Cheng, Cheng ^[1]; Chuang, Gwo-Yu ^[1];

^[1];

^[1]; O’Dell, Sijy ^[1]; Rawi, Reda ^[1]; Sastry, Mallika ^[1]; Shen, Chen-Hsiang ^[1]; Zhang, Baoshan ^[1]; Zhou, Tongqing ^[1]; Asokan, Mangaiarkarasi ^[1]; Bailer, Robert T. ^[1]; Chambers, Michael ^[1]; Chen, Xuejun ^[1]; Choi, Chang W. ^[1]; Dandey, Venkata P. ^[3]; Doria-Rose, Nicole A. ^[1] more »

National Inst. of Health (NIH), Bethesda, MD (United States)
National Inst. of Health (NIH), Bethesda, MD (United States); Simons Electron Microscopy Center, New York, NY (United States)
Simons Electron Microscopy Center, New York, NY (United States)
Vanderbilt Univ., Nashville, TN (United States)
Univ. of California, San Francisco, CA (United States)
Columbia Univ., New York, NY (United States)
Frederick National Lab for Cancer Research, Frederick, MD (United States)
GenScript USA, Piscataway, NJ (United States)
National Inst. of Health (NIH), Bethesda, MD (United States) ; Columbia Univ., New York, NY (United States)
National Inst. of Health (NIH), Bethesda, MD (United States); Columbia Univ., New York, NY (United States)

A central goal of HIV-1 vaccine research is the elicitation of antibodies capable of neutralizing diverse primary isolates of HIV-1. Here we show that focusing the immune response to exposed N-terminal residues of the fusion peptide, a critical component of the viral entry machinery and the epitope of antibodies elicited by HIV-1 infection, through immunization with fusion peptide-coupled carriers and prefusion stabilized envelope trimers, induces cross-clade neutralizing responses. In mice, these immunogens elicited monoclonal antibodies capable of neutralizing up to 31% of a cross-clade panel of 208 HIV-1 strains. Crystal and cryoelectron microscopy structures of these antibodies revealed fusion peptide conformational diversity as a molecular explanation for the cross-clade neutralization. Immunization of guinea pigs and rhesus macaques induced similarly broad fusion peptide-directed neutralizing responses, suggesting translatability. In conclusion, the N terminus of the HIV-1 fusion peptide is thus a promising target of vaccine efforts aimed at eliciting broadly neutralizing antibodies.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Basic Energy Sciences (BES); National Institutes of Health (NIH); Simons Foundation; National Institute of General Medical Sciences; Agouron Institute

Grant/Contract Number:: W-31-109-Eng-38; HHSN261200800001E; R01 AI131722; SF349247; GM103310; F00316; OD019994

OSTI ID:: 1467705

Journal Information:: Nature Medicine, Vol. 24, Issue 6; ISSN 1078-8956

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited by: 163 works

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References (82)

Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans Garces, Fernando; Lee, Jeong Hyun; de Val, Natalia Immunity, Vol. 43, Issue 6 https://doi.org/10.1016/j.immuni.2015.11.007	journal	December 2015
Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env Do Kwon, Young; Pancera, Marie; Acharya, Priyamvada Nature Structural & Molecular Biology, Vol. 22, Issue 7 https://doi.org/10.1038/nsmb.3051	journal	June 2015
Vaccine-Induced Antibodies that Neutralize Group 1 and Group 2 Influenza A Viruses Joyce, M. Gordon; Wheatley, Adam K.; Thomas, Paul V. Cell, Vol. 166, Issue 3 https://doi.org/10.1016/j.cell.2016.06.043	journal	July 2016
Delay of HIV-1 rebound after cessation of antiretroviral therapy through passive transfer of human neutralizing antibodies Trkola, Alexandra; Kuster, Herbert; Rusert, Peter Nature Medicine, Vol. 11, Issue 6 https://doi.org/10.1038/nm1244	journal	May 2005
Immunization-Elicited Broadly Protective Antibody Reveals Ebolavirus Fusion Loop as a Site of Vulnerability Zhao, Xuelian; Howell, Katie A.; He, Shihua Cell, Vol. 169, Issue 5 https://doi.org/10.1016/j.cell.2017.04.038	journal	May 2017
MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes Davis, I. W.; Murray, L. W.; Richardson, J. S. Nucleic Acids Research, Vol. 32, Issue Web Server https://doi.org/10.1093/nar/gkh398	journal	July 2004
A Virulence Locus of Pseudomonas aeruginosa Encodes a Protein Secretion Apparatus Mougous, J. D. Science, Vol. 312, Issue 5779 https://doi.org/10.1126/science.1128393	journal	June 2006
Antibodies from a Human Survivor Define Sites of Vulnerability for Broad Protection against Ebolaviruses Wec, Anna Z.; Herbert, Andrew S.; Murin, Charles D. Cell, Vol. 169, Issue 5 https://doi.org/10.1016/j.cell.2017.04.037	journal	May 2017
Dendroscope: An interactive viewer for large phylogenetic trees Huson, Daniel H.; Richter, Daniel C.; Rausch, Christian BMC Bioinformatics, Vol. 8, Issue 1 https://doi.org/10.1186/1471-2105-8-460	journal	November 2007
Broad and potent neutralization of HIV-1 by a gp41-specific human antibody Huang, Jinghe; Ofek, Gilad; Laub, Leo Nature, Vol. 491, Issue 7424 https://doi.org/10.1038/nature11544	journal	September 2012
Structure of HIV-1 gp120 V1/V2 domain with broadly neutralizing antibody PG9 McLellan, Jason S.; Pancera, Marie; Carrico, Chris Nature, Vol. 480, Issue 7377 https://doi.org/10.1038/nature10696	journal	November 2011
Relationship between Antibody 2F5 Neutralization of HIV-1 and Hydrophobicity of Its Heavy Chain Third Complementarity-Determining Region Ofek, G.; McKee, K.; Yang, Y. Journal of Virology, Vol. 84, Issue 6 https://doi.org/10.1128/JVI.02257-09	journal	December 2009
Broad neutralization coverage of HIV by multiple highly potent antibodies Walker, Laura M.; Huber, Michael; Doores, Katie J. Nature, Vol. 477, Issue 7365 https://doi.org/10.1038/nature10373	journal	September 2011
Structural Delineation of a Quaternary, Cleavage-Dependent Epitope at the gp41-gp120 Interface on Intact HIV-1 Env Trimers Blattner, Claudia; Lee, Jeong Hyun; Sliepen, Kwinten Immunity, Vol. 40, Issue 5 https://doi.org/10.1016/j.immuni.2014.04.008	journal	May 2014
HIV-1 neutralizing antibodies: understanding nature's pathways Mascola, John R.; Haynes, Barton F. Immunological Reviews, Vol. 254, Issue 1 https://doi.org/10.1111/imr.12075	journal	June 2013
Delineating Antibody Recognition in Polyclonal Sera from Patterns of HIV-1 Isolate Neutralization Georgiev, I. S.; Doria-Rose, N. A.; Zhou, T. Science, Vol. 340, Issue 6133 https://doi.org/10.1126/science.1233989	journal	May 2013
Sequence and Structural Convergence of Broad and Potent HIV Antibodies That Mimic CD4 Binding Scheid, J. F.; Mouquet, H.; Ueberheide, B. Science, Vol. 333, Issue 6049 https://doi.org/10.1126/science.1207227	journal	July 2011
Appion: An integrated, database-driven pipeline to facilitate EM image processing Lander, Gabriel C.; Stagg, Scott M.; Voss, Neil R. Journal of Structural Biology, Vol. 166, Issue 1 https://doi.org/10.1016/j.jsb.2009.01.002	journal	April 2009
Comparison of simple potential functions for simulating liquid water Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D. The Journal of Chemical Physics, Vol. 79, Issue 2 https://doi.org/10.1063/1.445869	journal	July 1983
A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but Not Non-Neutralizing Antibodies Sanders, Rogier W.; Derking, Ronald; Cupo, Albert PLoS Pathogens, Vol. 9, Issue 9, Article No. e1003618 https://doi.org/10.1371/journal.ppat.1003618	journal	September 2013
Human Peripheral Blood Antibodies with Long HCDR3s Are Established Primarily at Original Recombination Using a Limited Subset of Germline Genes Briney, Bryan S.; Willis, Jordan R.; Crowe, James E. PLoS ONE, Vol. 7, Issue 5 https://doi.org/10.1371/journal.pone.0036750	journal	May 2012
Keyhole limpet hemocyanin (KLH): a biomedical review Harris, J. R.; Markl∗, J. Micron, Vol. 30, Issue 6 https://doi.org/10.1016/S0968-4328(99)00036-0	journal	December 1999
A Blueprint for HIV Vaccine Discovery Burton, Dennis R.; Ahmed, Rafi; Barouch, Dan H. Cell Host & Microbe, Vol. 12, Issue 4 https://doi.org/10.1016/j.chom.2012.09.008	journal	October 2012
Antibody Recognition of a Highly Conserved Influenza Virus Epitope Ekiert, D. C.; Bhabha, G.; Elsliger, M. -A. Science, Vol. 324, Issue 5924 https://doi.org/10.1126/science.1171491	journal	April 2009
Rational Design of Envelope Identifies Broadly Neutralizing Human Monoclonal Antibodies to HIV-1 Wu, X.; Yang, Z. -Y.; Li, Y. Science, Vol. 329, Issue 5993 https://doi.org/10.1126/science.1187659	journal	July 2010
Structures of HIV-1 Env V1V2 with broadly neutralizing antibodies reveal commonalities that enable vaccine design Gorman, Jason; Soto, Cinque; Yang, Max M. Nature Structural & Molecular Biology, Vol. 23, Issue 1 https://doi.org/10.1038/nsmb.3144	journal	December 2015
Tiered Categorization of a Diverse Panel of HIV-1 Env Pseudoviruses for Assessment of Neutralizing Antibodies Seaman, M. S.; Janes, H.; Hawkins, N. Journal of Virology, Vol. 84, Issue 3 https://doi.org/10.1128/JVI.02108-09	journal	November 2009
Timing the Ancestor of the HIV-1 Pandemic Strains Korber, B. Science, Vol. 288, Issue 5472 https://doi.org/10.1126/science.288.5472.1789	journal	June 2000
Crystal structure of the TSP-1 type 1 repeats: a novel layered fold and its biological implication Tan, Kemin; Duquette, Mark; Liu, Jin-huan The Journal of Cell Biology, Vol. 159, Issue 2 https://doi.org/10.1083/jcb.200206062	journal	October 2002
UCSF Chimera?A visualization system for exploratory research and analysis Pettersen, Eric F.; Goddard, Thomas D.; Huang, Conrad C. Journal of Computational Chemistry, Vol. 25, Issue 13 https://doi.org/10.1002/jcc.20084	journal	January 2004
An HIV-1 antibody from an elite neutralizer implicates the fusion peptide as a site of vulnerability van Gils, Marit J.; van den Kerkhof, Tom L. G. M.; Ozorowski, Gabriel Nature Microbiology, Vol. 2, Issue 2 https://doi.org/10.1038/nmicrobiol.2016.199	journal	November 2016
HIV-1 neutralizing antibodies induced by native-like envelope trimers Sanders, R. W.; van Gils, M. J.; Derking, R. Science, Vol. 349, Issue 6244 https://doi.org/10.1126/science.aac4223	journal	June 2015
SPIDER and WEB: Processing and Visualization of Images in 3D Electron Microscopy and Related Fields Frank, Joachim; Radermacher, Michael; Penczek, Pawel Journal of Structural Biology, Vol. 116, Issue 1 https://doi.org/10.1006/jsbi.1996.0030	journal	January 1996
Gctf: Real-time CTF determination and correction Zhang, Kai Journal of Structural Biology, Vol. 193, Issue 1 https://doi.org/10.1016/j.jsb.2015.11.003	journal	January 2016
A Potent Cross-Clade Neutralizing Human Monoclonal Antibody against a Novel Epitope on gp41 of Human Immunodeficiency Virus Type 1 Stiegler, Gabriela; Kunert, Renate; Purtscher, Martin AIDS Research and Human Retroviruses, Vol. 17, Issue 18 https://doi.org/10.1089/08892220152741450	journal	December 2001
Redesign of a Four-helix Bundle Protein by Phage Display Coupled with Proteolysis and Structural Characterization by NMR and X-ray Crystallography Chu, Ruiai; Takei, Jiro; Knowlton, J. Randolph Journal of Molecular Biology, Vol. 323, Issue 2 https://doi.org/10.1016/S0022-2836(02)00884-7	journal	October 2002
Optimization and validation of the TZM-bl assay for standardized assessments of neutralizing antibodies against HIV-1 Sarzotti-Kelsoe, Marcella; Bailer, Robert T.; Turk, Ellen Journal of Immunological Methods, Vol. 409 https://doi.org/10.1016/j.jim.2013.11.022	journal	July 2014
Crystal Structure of Human Collagen XVIII Trimerization Domain: A Novel Collagen Trimerization Fold Boudko, Sergei P.; Sasaki, Takako; Engel, Jürgen Journal of Molecular Biology, Vol. 392, Issue 3 https://doi.org/10.1016/j.jmb.2009.07.057	journal	September 2009
Potent and broad neutralization of HIV-1 by a llama antibody elicited by immunization McCoy, Laura E.; Quigley, Anna Forsman; Strokappe, Nika M. The Journal of Experimental Medicine, Vol. 209, Issue 6 https://doi.org/10.1084/jem.20112655	journal	May 2012
EMAN2: An extensible image processing suite for electron microscopy Tang, Guang; Peng, Liwei; Baldwin, Philip R. Journal of Structural Biology, Vol. 157, Issue 1 https://doi.org/10.1016/j.jsb.2006.05.009	journal	January 2007
Immunogenicity of Stabilized HIV-1 Envelope Trimers with Reduced Exposure of Non-neutralizing Epitopes de Taeye, Steven W.; Ozorowski, Gabriel; Torrents de la Peña, Alba Cell, Vol. 163, Issue 7 https://doi.org/10.1016/j.cell.2015.11.056	journal	December 2015
Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target Walker, L. M.; Phogat, S. K.; Chan-Hui, P. -Y. Science, Vol. 326, Issue 5950 https://doi.org/10.1126/science.1178746	journal	September 2009
RELION: Implementation of a Bayesian approach to cryo-EM structure determination Scheres, Sjors H. W. Journal of Structural Biology, Vol. 180, Issue 3, p. 519-530 https://doi.org/10.1016/j.jsb.2012.09.006	journal	December 2012
EMRinger: side chain–directed model and map validation for 3D cryo-electron microscopy Barad, Benjamin A.; Echols, Nathaniel; Wang, Ray Yu-Ruei Nature Methods, Vol. 12, Issue 10 https://doi.org/10.1038/nmeth.3541	journal	August 2015
Reshaping Antibody Diversity Wang, Feng; Ekiert, Damian C.; Ahmad, Insha Cell, Vol. 153, Issue 6 https://doi.org/10.1016/j.cell.2013.04.049	journal	June 2013
Rapid elicitation of broadly neutralizing antibodies to HIV by immunization in cows Sok, Devin; Le, Khoa M.; Vadnais, Melissa Nature, Vol. 548, Issue 7665 https://doi.org/10.1038/nature23301	journal	July 2017
Elicitation of Robust Tier 2 Neutralizing Antibody Responses in Nonhuman Primates by HIV Envelope Trimer Immunization Using Optimized Approaches Pauthner, Matthias; Havenar-Daughton, Colin; Sok, Devin Immunity, Vol. 46, Issue 6 https://doi.org/10.1016/j.immuni.2017.05.007	journal	June 2017
Fusion peptide of HIV-1 as a site of vulnerability to neutralizing antibody Kong, R.; Xu, K.; Zhou, T. Science, Vol. 352, Issue 6287 https://doi.org/10.1126/science.aae0474	journal	May 2016
Discovery of an antibody for pan-ebolavirus therapy Furuyama, Wakako; Marzi, Andrea; Nanbo, Asuka Scientific Reports, Vol. 6, Issue 1 https://doi.org/10.1038/srep20514	journal	February 2016
A Potent and Broad Neutralizing Antibody Recognizes and Penetrates the HIV Glycan Shield Pejchal, R.; Doores, K. J.; Walker, L. M. Science, Vol. 334, Issue 6059 https://doi.org/10.1126/science.1213256	journal	October 2011
Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation Zhou, Tongqing; Doria-Rose, Nicole A.; Cheng, Cheng Cell Reports, Vol. 19, Issue 4 https://doi.org/10.1016/j.celrep.2017.04.013	journal	April 2017
Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors Zhou, Tongqing; Lynch, Rebecca M.; Chen, Lei Cell, Vol. 161, Issue 6 https://doi.org/10.1016/j.cell.2015.05.007	journal	June 2015
Structural basis for antibody-mediated neutralization of Lassa virus Hastie, Kathryn M.; Zandonatti, Michelle A.; Kleinfelter, Lara M. Science, Vol. 356, Issue 6341 https://doi.org/10.1126/science.aam7260	journal	June 2017
Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting Doria-Rose, Nicole A.; Altae-Tran, Han R.; Roark, Ryan S. PLOS Pathogens, Vol. 13, Issue 1 https://doi.org/10.1371/journal.ppat.1006148	journal	January 2017
Human Antibodies that Neutralize HIV-1: Identification, Structures, and B Cell Ontogenies Kwong, Peter D.; Mascola, John R. Immunity, Vol. 37, Issue 3 https://doi.org/10.1016/j.immuni.2012.08.012	journal	September 2012
Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120 Kong, Leopold; Lee, Jeong Hyun; Doores, Katie J. Nature Structural & Molecular Biology, Vol. 20, Issue 7 https://doi.org/10.1038/nsmb.2594	journal	May 2013
Identification of Common Features in Prototype Broadly Neutralizing Antibodies to HIV Envelope V2 Apex to Facilitate Vaccine Design Andrabi, Raiees; Voss, James E.; Liang, Chi-Hui Immunity, Vol. 43, Issue 5 https://doi.org/10.1016/j.immuni.2015.10.014	journal	November 2015
Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies Doria-Rose, Nicole A.; Schramm, Chaim A.; Gorman, Jason Nature, Vol. 509, Issue 7498 https://doi.org/10.1038/nature13036	journal	March 2014
Uncleaved prefusion-optimized gp140 trimers derived from analysis of HIV-1 envelope metastability Kong, Leopold; He, Linling; de Val, Natalia Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms12040	journal	June 2016
Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing Wu, X.; Zhou, T.; Zhu, J. Science, Vol. 333, Issue 6049 https://doi.org/10.1126/science.1207532	journal	August 2011
Crystallographic Identification of Lipid as an Integral Component of the Epitope of HIV Broadly Neutralizing Antibody 4E10 Irimia, Adriana; Sarkar, Anita; Stanfield, Robyn L. Immunity, Vol. 44, Issue 1 https://doi.org/10.1016/j.immuni.2015.12.001	journal	January 2016
Automated electron microscope tomography using robust prediction of specimen movements Mastronarde, David N. Journal of Structural Biology, Vol. 152, Issue 1 https://doi.org/10.1016/j.jsb.2005.07.007	journal	October 2005
A new method for vitrifying samples for cryoEM Razinkov, Ivan; Dandey, Venkata P.; Wei, Hui Journal of Structural Biology, Vol. 195, Issue 2 https://doi.org/10.1016/j.jsb.2016.06.001	journal	August 2016
cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination Punjani, Ali; Rubinstein, John L.; Fleet, David J. Nature Methods, Vol. 14, Issue 3 https://doi.org/10.1038/nmeth.4169	journal	February 2017
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Nanobodies: Natural Single-Domain Antibodies Muyldermans, Serge Annual Review of Biochemistry, Vol. 82, Issue 1 https://doi.org/10.1146/annurev-biochem-063011-092449	journal	June 2013
Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120 Chen, L.; Do Kwon, Y.; Zhou, T. Science, Vol. 326, Issue 5956 https://doi.org/10.1126/science.1175868	journal	November 2009
Optimizing “self-wicking” nanowire grids Wei, Hui; Dandey, Venkata P.; Zhang, Zhening Journal of Structural Biology, Vol. 202, Issue 2 https://doi.org/10.1016/j.jsb.2018.01.001	journal	May 2018
Mapping Polyclonal HIV-1 Antibody Responses via Next-Generation Neutralization Fingerprinting Doria-Rose, Nicole A.; Altae-Tran, Han R.; Roark, Ryan S. Columbia University https://doi.org/10.7916/d8zw1rks	text	January 2017
Preclinical Development of a Fusion Peptide Conjugate as an HIV Vaccine Immunogen Ou, Li; Kong, Wing-Pui; Chuang, Gwo-Yu Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-59711-y	journal	February 2020
Structural Repertoire of HIV-1-Neutralizing Antibodies Targeting the CD4 Supersite in 14 Donors Aliaksandr, Druz,; F., Scheid, Johannes; R., Burton, Dennis The University of North Carolina at Chapel Hill University Libraries https://doi.org/10.17615/gy1k-dg87	text	January 2015
In vivo efficacy of human immunodeficiency virus neutralizing antibodies: estimates for protective titers Trkola, A.; Kuster, H.; Rusert, P. American Society for Microbiology https://doi.org/10.5167/uzh-5468	text	January 2008
A spring-loaded mechanism for the conformational change of influenza hemagglutinin Carr, Chavela M.; Kim, Peter S. Cell, Vol. 73, Issue 4 https://doi.org/10.1016/0092-8674(93)90260-w	journal	May 1993
Positional effect of single bulge nucleotide on PNA(peptide nucleic acid)/DNA hybrid stability Sugimoto, N.; Yamamoto, K.; Satoh, N. Nucleic Acids Symposium Series, Vol. 42, Issue 1 https://doi.org/10.1093/nass/42.1.95	journal	November 1999
Recent developments in the PHENIX software for automated crystallographic structure determination Adams, Paul D.; Gopal, Kreshna; Grosse-Kunstleve, Ralf W. Journal of Synchrotron Radiation, Vol. 11, Issue 1 https://doi.org/10.1107/s0909049503024130	journal	November 2003
In Vivo Efficacy of Human Immunodeficiency Virus Neutralizing Antibodies: Estimates for Protective Titers Trkola, A.; Kuster, H.; Rusert, P. Journal of Virology, Vol. 82, Issue 3 https://doi.org/10.1128/jvi.01792-07	journal	November 2007
Structure-Guided Redesign Increases the Propensity of HIV Env To Generate Highly Stable Soluble Trimers Guenaga, Javier; Dubrovskaya, Viktoriya; de Val, Natalia Journal of Virology, Vol. 90, Issue 6 https://doi.org/10.1128/jvi.02652-15	journal	December 2015
A conserved neutralizing epitope on gp41 of human immunodeficiency virus type 1. Muster, T.; Steindl, F.; Purtscher, M. Journal of Virology, Vol. 67, Issue 11 https://doi.org/10.1128/jvi.67.11.6642-6647.1993	journal	January 1993
Cross-neutralizing activity against divergent human immunodeficiency virus type 1 isolates induced by the gp41 sequence ELDKWAS. Muster, T.; Guinea, R.; Trkola, A. Journal of Virology, Vol. 68, Issue 6 https://doi.org/10.1128/jvi.68.6.4031-4034.1994	journal	January 1994
Human monoclonal antibody 2G12 defines a distinctive neutralization epitope on the gp120 glycoprotein of human immunodeficiency virus type 1. Trkola, A.; Purtscher, M.; Muster, T. Journal of virology, Vol. 70, Issue 2 https://doi.org/10.1128/jvi.70.2.1100-1108.1996	journal	January 1996
Structure and Mechanistic Analysis of the Anti-Human Immunodeficiency Virus Type 1 Antibody 2F5 in Complex with Its gp41 Epitope Ofek, G.; Tang, M.; Sambor, A. Journal of Virology, Vol. 78, Issue 19 https://doi.org/10.1128/jvi.78.19.10724-10737.2004	journal	September 2004
Antibody polyspecificity and neutralization of HIV-1: A hypothesis Haynes, Barton F.; Moody, M. Anthony; Verkoczy, Laurent Human Antibodies, Vol. 14, Issue 3-4 https://doi.org/10.3233/hab-2005-143-402	journal	May 2006

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Clade C HIV-1 Envelope Vaccination Regimens Differ in Their Ability To Elicit Antibodies with Moderate Neutralization Breadth against Genetically Diverse Tier 2 HIV-1 Envelope Variants Burton, Samantha; Spicer, Lori M.; Charles, Tysheena P. Journal of Virology, Vol. 93, Issue 7 https://doi.org/10.1128/jvi.01846-18	journal	January 2019
The Polar Region of the HIV-1 Envelope Protein Determines Viral Fusion and Infectivity by Stabilizing the gp120-gp41 Association Lu, Wuxun; Chen, Shuliang; Yu, Jingyou Journal of Virology, Vol. 93, Issue 7 https://doi.org/10.1128/jvi.02128-18	journal	January 2019
Reverse Immunology Approach to Define a New HIV-gp41-Neutralizing Epitope Dorgham, Karim; Pietrancosta, Nicolas; Affoune, Amel Journal of Immunology Research, Vol. 2019 https://doi.org/10.1155/2019/9804584	journal	March 2019
HIV-1 immunogens and strategies to drive antibody responses towards neutralization breadth van Schooten, Jelle; van Gils, Marit J. Retrovirology, Vol. 15, Issue 1 https://doi.org/10.1186/s12977-018-0457-7	journal	November 2018
Star nanoparticles delivering HIV-1 peptide minimal immunogens elicit near-native envelope antibody responses in nonhuman primates Francica, Joseph R.; Laga, Richard; Lynn, Geoffrey M. PLOS Biology, Vol. 17, Issue 6 https://doi.org/10.1371/journal.pbio.3000328	journal	June 2019
Optimizing the production and affinity purification of HIV-1 envelope glycoprotein SOSIP trimers from transiently transfected CHO cells Cupo, Albert; Cruz Portillo, Victor M.; Gelfand, Paul PLOS ONE, Vol. 14, Issue 4 https://doi.org/10.1371/journal.pone.0215106	journal	April 2019
Identification of variant HIV envelope proteins with enhanced affinities for precursors to anti-gp41 broadly neutralizing antibodies Zhu, Hong; Mathew, Elizabeth; Connelly, Sara M. PLOS ONE, Vol. 14, Issue 9 https://doi.org/10.1371/journal.pone.0221550	journal	September 2019
Complete functional mapping of infection- and vaccine-elicited antibodies against the fusion peptide of HIV Dingens, Adam S.; Acharya, Priyamvada; Haddox, Hugh K. PLOS Pathogens, Vol. 14, Issue 7 https://doi.org/10.1371/journal.ppat.1007159	journal	July 2018
Neutralization-guided design of HIV-1 envelope trimers with high affinity for the unmutated common ancestor of CH235 lineage CD4bs broadly neutralizing antibodies LaBranche, Celia C.; Henderson, Rory; Hsu, Allen PLOS Pathogens, Vol. 15, Issue 9 https://doi.org/10.1371/journal.ppat.1008026	journal	September 2019
Computationally Designed Peptides for Zika Virus Detection: An Incremental Construction Approach Mascini, Marcello; Dikici, Emre; Robles Mañueco, Marta Biomolecules, Vol. 9, Issue 9 https://doi.org/10.3390/biom9090498	journal	September 2019
T = 4 Icosahedral HIV-1 Capsid As an Immunogenic Vector for HIV-1 V3 Loop Epitope Display Zhang, Zhiqing; He, Maozhou; Bai, Shimeng Viruses, Vol. 10, Issue 12 https://doi.org/10.3390/v10120667	journal	November 2018
Development of Antibodies with Broad Neutralization Specificities against HIV-1 after Long Term SHIV Infection in Macaques Gao, Nan; Gai, Yanxin; Meng, Lina Viruses, Vol. 12, Issue 2 https://doi.org/10.3390/v12020163	journal	January 2020
Artificial Anti-HIV-1 Immunogen Comprising Epitopes of Broadly Neutralizing Antibodies 2F5, 10E8, and a Peptide Mimic of VRC01 Discontinuous Epitope Rudometov, Andrey P.; Chikaev, Anton N.; Rudometova, Nadezhda B. Vaccines, Vol. 7, Issue 3 https://doi.org/10.3390/vaccines7030083	journal	August 2019
Viral Vectors for the Induction of Broadly Neutralizing Antibodies against HIV Wilmschen, Sarah; Schmitz, Joern E.; Kimpel, Janine Vaccines, Vol. 7, Issue 3 https://doi.org/10.3390/vaccines7030119	journal	September 2019
Germline VRC01 antibody recognition of a modified clade C HIV-1 envelope trimer and a glycosylated HIV-1 gp120 core Borst, Andrew J.; Weidle, Connor E.; Gray, Matthew D. eLife, Vol. 7 https://doi.org/10.7554/elife.37688	journal	November 2018
Protein denaturation at the air-water interface and how to prevent it D'Imprima, Edoardo; Floris, Davide; Joppe, Mirko eLife, Vol. 8 https://doi.org/10.7554/elife.42747	journal	April 2019
Improvement of antibody functionality by structure-guided paratope engraftment Liu, Qingbo; Lai, Yen-Ting; Zhang, Peng Nature Communications, Vol. 10, Issue 1 https://doi.org/10.1038/s41467-019-08658-4	journal	February 2019
Characterization of the furin cleavage motif for HIV-1 trimeric envelope glycoprotein by intact LC-MS analysis Schneck, Nicole A.; Ivleva, Vera B.; Cai, Cindy X. The Analyst, Vol. 145, Issue 5 https://doi.org/10.1039/c9an02098e	journal	January 2020
Poly- and autoreactivity of HIV-1 bNAbs: implications for vaccine design Finney, Joel; Kelsoe, Garnett Retrovirology, Vol. 15, Issue 1 https://doi.org/10.1186/s12977-018-0435-0	journal	July 2018
Consistent elicitation of cross-clade HIV-neutralizing responses achieved in guinea pigs after fusion peptide priming by repetitive envelope trimer boosting Cheng, Cheng; Xu, Kai; Kong, Rui PLOS ONE, Vol. 14, Issue 4 https://doi.org/10.1371/journal.pone.0215163	journal	April 2019
Quantification of the Resilience and Vulnerability of HIV-1 Native Glycan Shield at Atomistic Detail Chakraborty, Srirupa; Berndsen, Zachary T.; Hengartner, Nicolas W. SSRN Electronic Journal https://doi.org/10.2139/ssrn.3606299	journal	January 2020
Advancing an HIV vaccine; advancing vaccinology Burton, Dennis R. Nature Reviews Immunology, Vol. 19, Issue 2 https://doi.org/10.1038/s41577-018-0103-6	journal	December 2018
Boosting subdominant neutralizing antibody responses with a computationally designed epitope-focused immunogen Sesterhenn, Fabian; Galloux, Marie; Vollers, Sabrina S. PLOS Biology, Vol. 17, Issue 2 https://doi.org/10.1371/journal.pbio.3000164	journal	February 2019
Development of antibodies with broad neutralization specificities against HIV-1 after long term SHIV infection in macaques Nan, Gao; Yanxin, Gai; Lina, Meng Zenodo https://doi.org/10.5281/zenodo.3608718	text	January 2020
Gene Editing of HIV-1 Co-receptors to Prevent and/or Cure Virus Infection Allen, Alexander G.; Chung, Cheng-Han; Atkins, Andrew Frontiers in Microbiology, Vol. 9 https://doi.org/10.3389/fmicb.2018.02940	journal	December 2018
Boosting subdominant neutralizing antibody responses with a computationally designed epitope-focused immunogen Fabian, Sesterhenn,; Marie, Galloux,; Lucia, Csepregi, ETH Zurich https://doi.org/10.3929/ethz-b-000331744	text	January 2019
Development of antibodies with broad neutralization specificities against HIV-1 after long term SHIV infection in macaques Nan, Gao; Yanxin, Gai; Lina, Meng Zenodo https://doi.org/10.5281/zenodo.3608719	text	January 2020
HIV / AIDS Vaccines: 2018 Robinson, Harriet L. Clinical Pharmacology & Therapeutics, Vol. 104, Issue 6 https://doi.org/10.1002/cpt.1208	journal	October 2018
The Chimpanzee SIV Envelope Trimer: Structure and Deployment as an HIV Vaccine Template Andrabi, Raiees; Pallesen, Jesper; Allen, Joel D. Cell Reports, Vol. 27, Issue 8 https://doi.org/10.1016/j.celrep.2019.04.082	journal	May 2019
Vaccination with Glycan-Modified HIV NFL Envelope Trimer-Liposomes Elicits Broadly Neutralizing Antibodies to Multiple Sites of Vulnerability Dubrovskaya, Viktoriya; Tran, Karen; Ozorowski, Gabriel Immunity, Vol. 51, Issue 5 https://doi.org/10.1016/j.immuni.2019.10.008	journal	November 2019
Peptide-Based Vaccines: Current Progress and Future Challenges Malonis, Ryan J.; Lai, Jonathan R.; Vergnolle, Olivia Chemical Reviews, Vol. 120, Issue 6 https://doi.org/10.1021/acs.chemrev.9b00472	journal	December 2019
The Impact of Sustained Immunization Regimens on the Antibody Response to Oligomannose Glycans Nguyen, Dung N.; Redman, Richard L.; Horiya, Satoru ACS Chemical Biology, Vol. 15, Issue 3 https://doi.org/10.1021/acschembio.0c00053	journal	February 2020
HIV-1 cell-to-cell transmission and broadly neutralizing antibodies Dufloo, Jérémy; Bruel, Timothée; Schwartz, Olivier Retrovirology, Vol. 15, Issue 1 https://doi.org/10.1186/s12977-018-0434-1	journal	July 2018
Stabilizing HIV-1 envelope glycoprotein trimers to induce neutralizing antibodies Torrents de la Peña, Alba; Sanders, Rogier W. Retrovirology, Vol. 15, Issue 1 https://doi.org/10.1186/s12977-018-0445-y	journal	September 2018
Immune Protection of SIV Challenge by PD-1 Blockade During Vaccination in Rhesus Monkeys Pan, Enxiang; Feng, Fengling; Li, Pingchao Frontiers in Immunology, Vol. 9 https://doi.org/10.3389/fimmu.2018.02415	journal	October 2018

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