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HIV-1 vaccine design by serving as templates for bnAb-eliciting vaccines. Since single Env-based immunizations are insufficient to induce bnAb responses, sequential regimens using multivalent immunogens or Env cocktails hold greater promise. This underscores the need to develop stable Env trimers from diverse HIV-1 strains, particularly clade-C, which accounts for 50% of global infections and over 90% in India and South Africa. While various platforms exist to stabilize soluble Env trimers for use as antigenic baits and vaccines, stabilizing clade C trimers remains challenging. Methods: We stabilized an HIV-1 clade C trimer based on an Env isolated from a pediatric elite neutralizer (AIIMS_329) using multiple platforms, including SOSIP.v8.2, ferritin nanoparticles (NPs) and I53-50 two-component NPs, followed by characterization of their biophysical, antigenic, and immunogenic properties. Results: The stabilized 329 Envs showed binding to multiple HIV-1 bnAbs, with negligible binding to non-neutralizing antibodies. Negative-stain electron microscopy confirmed the native-like conformation of the Envs. Multimerization of 329 SOSIP.v8.2 on ferritin and two-component I53-50 NPs improved the affinity to HIV-1 bnAbs and showed higher immunogenicity in rabbits. Conclusions: The soluble 329 Env protein could serve as an antigenic bait, and multimeric 329 NP Envs are potential vaccine candidates.<\/jats:p>","DOI":"10.3390\/vaccines13020110","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T12:19:55Z","timestamp":1737548395000},"page":"110","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Design and Immunogenicity of an HIV-1 Clade C Pediatric Envelope Glycoprotein Stabilized by Multiple Platforms"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8181-3999","authenticated-orcid":false,"given":"Sanjeev","family":"Kumar","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India"},{"name":"Department of Pediatrics, Division of Infectious Diseases, Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6356-1484","authenticated-orcid":false,"given":"Iv\u00e1n del","family":"Moral-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Institute for Infection and Immunity, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1186-1327","authenticated-orcid":false,"given":"Swarandeep","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maddy L.","family":"Newby","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel D.","family":"Allen","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom P. L.","family":"Bijl","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Amsterdam Institute for Infection and Immunity, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yog","family":"Vaghani","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0194-4022","authenticated-orcid":false,"given":"Liang","family":"Jing","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rakesh","family":"Lodha","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8855-3029","authenticated-orcid":false,"given":"Eric A.","family":"Ortlund","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1072-2694","authenticated-orcid":false,"given":"Max","family":"Crispin","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, University of Southampton, Southampton SO17 1BJ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4760-9019","authenticated-orcid":false,"given":"Anamika","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rogier W.","family":"Sanders","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"},{"name":"Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10065, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7801-2867","authenticated-orcid":false,"given":"Kalpana","family":"Luthra","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, All India Institute of Medical Sciences, New Delhi 110029, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/S1473-3099(18)30647-9","article-title":"Global and Regional Molecular Epidemiology of HIV-1, 1990\u20132015: A Systematic Review, Global Survey, and Trend Analysis","volume":"19","author":"Hemelaar","year":"2019","journal-title":"Lancet Infect. 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