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Native-like HIV envelope (Env) trimers in a closed conformation represent promising immunogens. We evaluated the immunogenicity of the chimeric vesicular stomatitis virus-based vector VSV-GP encoding clade C membrane-tethered native-like trimers in heterologous prime\/boost combinations with autologous protein. Infected cells displayed high levels of native-like trimers on the surface in a favorable conformation and native-like trimers were also efficiently incorporated into VSV-GP particles. Heterologous vector\/protein immunizations outperformed homologous vector regimens, regardless of administration order. In rabbits, these regimens elicited Tier 1 and autologous Tier 2 neutralizing antibodies. Tier 2 neutralization was restricted to pseudoviruses matching the engineered Env-immunogen, with no cross-neutralization of parental Env-variants. Our findings support the use of VSV-GP as a potent platform for displaying native-like Env-trimers and highlight its potential in prime-boost strategies for HIV vaccine development.<\/jats:p>","DOI":"10.1038\/s41541-025-01334-3","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T06:18:39Z","timestamp":1765779519000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heterologous combinations of VSV-GP and native-like trimers elicit autologous Tier 2 HIV antibodies in rabbits"],"prefix":"10.1038","volume":"11","author":[{"given":"Frederik","family":"Radvan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Hauser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li-Yun","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Wilmschen-Tober","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marion","family":"Schaber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Bermejo-Jambrina","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tariq Oluwakunmi","family":"Agbabiaka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Peterhoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lydia","family":"Riepler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadja","family":"Mendrzyk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Beierfu\u00df","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia","family":"Speth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0916-156X","authenticated-orcid":false,"given":"Christiane","family":"Moog","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothee","family":"von Laer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ralf","family":"Wagner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-7905","authenticated-orcid":false,"given":"Janine","family":"Kimpel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,15]]},"reference":[{"key":"1334_CR1","unstructured":"UNAIDS. 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