{ "abstract": "Introduction: The envelope (Env) glycoproteins derived from circulating viruses in elite-neutralizers (ENs), who naturally develop potent broadly neutralizing antibody (bnAb) responses, serve as a potential template for HIV-1 vaccine design. Here, we investigated the immunogenicity and structure of a clade C HIV-1 Env trimer (330) derived from the pediatric elite-neutralizer AIIMS_330.\n\nMethods: The 330 Env was engineered as SOSIP.664, NFL.664, and multivalent ferritin-nanoparticle (NP) immunogens. Biophysical and antigenic properties were assessed using HIV-1 trimer-specific bnAbs and non-neutralizing antibodies. Immunogenicity was evaluated in rabbits immunized with Addavax-formulated SOSIP.664, NFL.664, or ferritin NP immunogens (n = 4), with an adjuvant only placebo group (n = 2). Structural characterization was performed by cryo-electron-microscopy (cryo-EM) using the autologous Env 330 SOSIP.664 trimer in complex with the bnAb 44m.\n\nResults: The 330 Env trimers exhibited native-like antigenic properties, high thermostability, strong binding to trimer-specific bnAbs, and limited reactivity with non-neutralizing antibodies. Immunization of rabbits elicited strong autologous neutralizing antibody responses together with modest heterologous Tier-1 neutralization. Autologous neutralizing responses were significantly higher for ferritin-NP (P = 0.019) and SOSIP.664 (P = 0.048) than for NFL.664, with no significant difference between ferritin-NP and SOSIP.664 (P = 0.681). A 5.1 Å cryo-EM reconstruction of the autologous Env 330 SOSIP.664–44m complex revealed native-like presentation of the N332-V3 supersite. The structural analysis further suggested the interacting Env contacts E293, R327, K337, and K446, along with glycans N332, N326, N442, and N448 with the bnAb-44m. We identified R327 of the conserved GDIR-motif and the N332 glycan, within the V3-loop, as neutralizing determinants on the 330 Env, with a fold reduction of 116, on testing the mutant 330 viruses with autologous bnAb 44m.\n\nDiscussion: Pediatric elite-neutralizer AIIMS_330 derived Env trimers represent structurally and antigenically well-characterized clade C immunogens with ability to elicit strong autologous neutralizing antibodies, with modest heterologous Tier-1 neutralization. Together, these findings advance our understanding of clade C Env antigenic variability. Further, the structural and immunological insights support the potential utility of AIIMS_330 derived Env as an antigenic probe and may inform future rational design of Clade C HIV-1 vaccines and structure-guided strategies for eliciting neutralizing antibodies.", "abstract_shown": true, "affiliations": [ "Department of Biochemistry, All India Institute of Medical Sciences", "Molecular Biophysics Unit, Indian Institute of Science", "Department of Biophysics, All India Institute of Medical Sciences", "Centralized Core Research Facility, All India Institute of Medical Sciences", "Department of Biosciences and Bioengineering, Indian Institute of Technology", "Department of Pediatrics, All India Institute of Medical Sciences" ], "article_type": "research article", "arxiv": null, "author_total": 21, "authors": [ { "affs": [ 0 ], "name": "Swarandeep Singh" }, { "affs": [ 0 ], "name": "Sanjeev Kumar" }, { "affs": [ 1 ], "name": "Arnab Chatterjee" }, { "affs": [ 2 ], "name": "Lakshay Malhotra" }, { "affs": [ 0 ], "name": "Muneeb Pervez" }, { "affs": [ 0 ], "name": "Abdul Rahman" }, { "affs": [ 0 ], "name": "Ifrah Andrabi" }, { "affs": [ 1 ], "name": "Bapan Mondal" }, { "affs": [ 0 ], "name": "Sanket Katpara" }, { "affs": [ 0 ], "name": "Shaifali Sharma" }, { "affs": [ 0 ], "name": "Harsh Bhakhri" }, { "affs": [ 0 ], "name": "Anjli Gaur" }, { "affs": [ 0 ], "name": "Tanu Bansal" }, { "affs": [ 0 ], "name": "Vikram Iyer" }, { "affs": [ 0 ], "name": "Abdul Wahid Hussain" }, { "affs": [ 3 ], "name": "Shubbir Ahmed" }, { "affs": [ 4 ], "name": "Rajesh Kumar" }, { "affs": [ 2 ], "name": "Abdul Samath Ethayathulla" }, { "affs": [ 5 ], "name": "Rakesh Lodha" }, { "affs": [ 1 ], "name": "Somnath Dutta" }, { "affs": [ 0 ], "name": "Kalpana Luthra" } ], "bibtex": "https://research.draconitic.com/paper/0892s41cr6p6t.bib", "cited_by": 0, "doi": "10.3389/fimmu.2026.1919627", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13731313/", "id": "0892s41cr6p6t", "issns": [ "1664-3224" ], "landing_url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1919627/full", "language": "en", "licence": "CC-BY-4.0", "licence_label": "CC BY 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Original Research" ], [ "openalex", "2406|HIV Research and Treatment" ] ], "openalex": "W7223129490", "pdf_url": null, "pmcid": "PMC13731313", "pmid": "42984752", "published": "2026-10-21", "publisher": "Frontiers Media SA", "ris": "https://research.draconitic.com/paper/0892s41cr6p6t.ris", "sources": [ { "first_seen": "2026-10-30T12:19:17Z", "native_id": "10.3389/fimmu.2026.1919627", "source": "crossref", "url": "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1919627/full" }, { "first_seen": "2026-11-08T12:21:32Z", "native_id": "PMC13731313", "source": "pmc", "url": "https://doi.org/10.3389/fimmu.2026.1919627" } ], "subjects": [ { "field": "biology", "origin": "openalex:2406|HIV Research and Treatment", "subfield": "microbiology" } ], "title": "Immunogenicity and structure of a stabilized HIV-1 clade C Env from a pediatric elite neutralizer in complex with an autologous bnAb", "title_text": "Immunogenicity and structure of a stabilized HIV-1 clade C Env from a pediatric elite neutralizer in complex with an autologous bnAb", "type": "peer-reviewed", "updated_at": "2026-11-08T12:21:32Z", "url": "https://research.draconitic.com/paper/0892s41cr6p6t", "venue": "Frontiers in Immunology", "versions": [] }