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To explore this premise, we conducted an immunization study in rhesus macaques (RM) using T\/F Env sequences from two human subjects, one of whom developed potent and broad neutralizing antibodies (Z1800M) while the other developed little to no neutralizing antibody responses (R66M) during HIV-1 infection. Using a DNA\/MVA\/protein immunization protocol, 10 RM were immunized with each T\/F Env. Within each T\/F Env group, the protein boosts were administered as either monomeric gp120 or stabilized trimeric gp140 protein. All vaccination regimens elicited high titers of antigen-specific IgG, and two animals that received monomeric Z1800M Env gp120 developed autologous neutralizing activity. Using early Env escape variants isolated from subject Z1800M as guides, the serum neutralizing activity of the two immunized RM was found to be dependent on the gp120 V5 region. Interestingly, the exact same residues of V5 were also targeted by a neutralizing monoclonal antibody (nmAb) isolated from the subject Z1800M early in infection. Glycan profiling and computational modeling of the Z1800M Env gp120 immunogen provided further evidence that the V5 loop is exposed in this T\/F Env and was a dominant feature that drove neutralizing antibody targeting during infection and immunization. An expanded B cell clonotype was isolated from one of the neutralization-positive RM and nmAbs corresponding to this group demonstrated V5-dependent neutralization similar to both the RM serum and the human Z1800M nmAb. The results demonstrate that neutralizing antibody responses elicited by the Z1800M T\/F Env in RM converged with those in the HIV-1 infected human subject, illustrating the potential of using immunogens based on this or other T\/F Envs with well-defined immunogenicity as a starting point to drive breadth.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010488","type":"journal-article","created":{"date-parts":[[2022,5,3]],"date-time":"2022-05-03T13:30:06Z","timestamp":1651584606000},"page":"e1010488","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["A neutralizing antibody target in early HIV-1 infection was recapitulated in rhesus macaques immunized with the transmitted\/founder envelope sequence"],"prefix":"10.1371","volume":"18","author":[{"given":"Sarah","family":"Welbourn","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srirupa","family":"Chakraborty","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie E.","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne S.","family":"Gleinich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sailaja","family":"Gangadhara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salar","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Ferrebee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhrugu","family":"Yagnik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Burton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tysheena","family":"Charles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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Spencer","year":"2021","journal-title":"Journal of immunology"},{"issue":"7723","key":"ppat.1010488.ref060","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/s41586-018-0517-0","article-title":"Tracing HIV-1 strains that imprint broadly neutralizing antibody responses","volume":"561","author":"RD Kouyos","year":"2018","journal-title":"Nature"},{"issue":"1","key":"ppat.1010488.ref061","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.celrep.2015.12.017","article-title":"Structural Constraints of Vaccine-Induced Tier-2 Autologous HIV Neutralizing Antibodies Targeting the Receptor-Binding Site","volume":"14","author":"T Bradley","year":"2016","journal-title":"Cell reports"},{"issue":"10","key":"ppat.1010488.ref062","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1016\/j.celrep.2015.05.017","article-title":"Structural Constraints Determine the Glycosylation of HIV-1 Envelope Trimers","volume":"11","author":"LK Pritchard","year":"2015","journal-title":"Cell reports"},{"issue":"6","key":"ppat.1010488.ref063","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1002\/cpt.1208","article-title":"HIV\/AIDS Vaccines: 2018","volume":"104","author":"HL Robinson","year":"2018","journal-title":"Clin Pharmacol Ther"},{"issue":"5","key":"ppat.1010488.ref064","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1016\/j.cell.2019.04.012","article-title":"Slow Delivery Immunization Enhances HIV Neutralizing Antibody and Germinal Center Responses via Modulation of Immunodominance","volume":"177","author":"KM Cirelli","year":"2019","journal-title":"Cell"},{"issue":"5","key":"ppat.1010488.ref065","article-title":"Gp120 V5 Is Targeted by the First Wave of Sequential Neutralizing Antibodies in SHIVSF162P3N-Infected Rhesus Macaques","volume":"10","author":"M Jia","year":"2018","journal-title":"Viruses"},{"issue":"22","key":"ppat.1010488.ref066","doi-asserted-by":"crossref","first-page":"10220","DOI":"10.1128\/JVI.01357-16","article-title":"Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site","volume":"90","author":"CK Wibmer","year":"2016","journal-title":"Journal of virology"},{"issue":"28","key":"ppat.1010488.ref067","doi-asserted-by":"crossref","first-page":"10275","DOI":"10.1073\/pnas.1409954111","article-title":"Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains","volume":"111","author":"D Fera","year":"2014","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"51","key":"ppat.1010488.ref068","doi-asserted-by":"crossref","first-page":"43170","DOI":"10.1074\/jbc.M112.399402","article-title":"A single residue within the V5 region of HIV-1 envelope 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Dingens","year":"2021","journal-title":"Elife"},{"issue":"1","key":"ppat.1010488.ref071","doi-asserted-by":"crossref","first-page":"e1000274","DOI":"10.1371\/journal.ppat.1000274","article-title":"Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1","volume":"5","author":"RE Haaland","year":"2009","journal-title":"PLoS pathogens"},{"issue":"1","key":"ppat.1010488.ref072","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1089\/aid.2010.0030","article-title":"Transmitted HIV type 1 drug resistance among individuals with recent HIV infection in East and Southern Africa","volume":"27","author":"MA Price","year":"2011","journal-title":"AIDS research and human retroviruses"},{"issue":"1","key":"ppat.1010488.ref073","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1093\/infdis\/jir199","article-title":"Prevention of infection by a granulocyte-macrophage colony-stimulating factor co-expressing DNA\/modified 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Barouch","year":"2005","journal-title":"J Virol"},{"issue":"7365","key":"ppat.1010488.ref082","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1038\/nature10373","article-title":"Broad neutralization coverage of HIV by multiple highly potent antibodies","volume":"477","author":"LM Walker","year":"2011","journal-title":"Nature"},{"issue":"11","key":"ppat.1010488.ref083","doi-asserted-by":"crossref","first-page":"5211","DOI":"10.1128\/JVI.00201-06","article-title":"Evidence for potent autologous neutralizing antibody titers and compact envelopes in early infection with subtype C human immunodeficiency virus type 1","volume":"80","author":"B Li","year":"2006","journal-title":"Journal of virology"},{"issue":"2","key":"ppat.1010488.ref084","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1128\/JVI.02006-10","article-title":"The B cell response is redundant and highly focused on V1V2 during early subtype C infection in a Zambian seroconverter","volume":"85","author":"RM Lynch","year":"2011","journal-title":"Journal of virology"},{"issue":"2","key":"ppat.1010488.ref085","doi-asserted-by":"crossref","first-page":"e1003173","DOI":"10.1371\/journal.ppat.1003173","article-title":"Viral escape from neutralizing antibodies in early subtype A HIV-1 infection drives an increase in autologous neutralization breadth","volume":"9","author":"MK Murphy","year":"2013","journal-title":"PLoS pathogens"},{"issue":"15","key":"ppat.1010488.ref086","doi-asserted-by":"crossref","first-page":"8031","DOI":"10.1128\/JVI.00771-12","article-title":"B-Lymphocyte Dysfunction in Chronic HIV-1 Infection Does Not Prevent Cross-Clade Neutralization Breadth","volume":"86","author":"S Boliar","year":"2012","journal-title":"Journal of virology"},{"issue":"7","key":"ppat.1010488.ref087","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.01846-18","article-title":"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","volume":"93","author":"S Burton","year":"2019","journal-title":"J Virol"},{"issue":"34","key":"ppat.1010488.ref088","doi-asserted-by":"crossref","first-page":"10780","DOI":"10.1073\/pnas.1509731112","article-title":"Breakthrough of SIV strain smE660 challenge in SIV strain mac239-vaccinated rhesus macaques despite potent autologous neutralizing antibody responses","volume":"112","author":"SL Burton","year":"2015","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"5666","key":"ppat.1010488.ref089","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1126\/science.1093137","article-title":"Envelope-Constrained Neutralization-Sensitive HIV-1 After Heterosexual Transmission","volume":"303","author":"CA Derdeyn","year":"2004","journal-title":"Science"},{"issue":"16","key":"ppat.1010488.ref090","doi-asserted-by":"crossref","first-page":"8130","DOI":"10.1128\/JVI.01221-14","article-title":"Characterization and Implementation of a Diverse Simian Immunodeficiency Virus SIVsm Envelope Panel in the Assessment of Neutralizing Antibody Breadth Elicited in Rhesus Macaques by Multimodal Vaccines Expressing the SIVmac239 Envelope","volume":"89","author":"KM Kilgore","year":"2015","journal-title":"Journal of virology"},{"issue":"12","key":"ppat.1010488.ref091","doi-asserted-by":"crossref","first-page":"6248","DOI":"10.1128\/JVI.00295-10","article-title":"Nonpathogenic simian immunodeficiency virus infection of sooty mangabeys is not associated with high levels of autologous neutralizing antibodies","volume":"84","author":"B Li","year":"2010","journal-title":"Journal of 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