biostudies-literatureUnknownChawla HRNA-based vaccines have emerged as a highly effective delivery platform. However, this approach eliminates the possibility for immunogen purification, common in manufacturing of recombinant immunogens. In HIV-1 vaccine design, this is of particular importance because non-native epitopes can compromise the desired immune response, and native immunogen assembly is important for presentation of glycan-based epitopes targeted by broadly neutralizing antibodies. Here, we investigate the assembly and glycosylation of the archetypal trimeric HIV-1 immunogen, BG505, in the soluble single-chain format (NFL.664) that bypasses the need of maturation by furin cleavage. We have investigated the presence of the trimer-associated mannose-patch as oligomannose-type structures at these <i>N</i>-linked glycRSC chemical biologyhttps://www.ebi.ac.uk/biostudies/studies/S-EPMC12853648biostudies-literatureSignatures of native-like glycosylation in RNA replicon-derived HIV-1 immunogens.PMC12853648Mckay PFIrvine DJOzorowski GChawla HSilva MHayes GMButler JWillcox JTLee WHWard ABShattock RJCrispin MfalseSignatures of native-like glycosylation in RNA replicon-derived HIV-1 immunogens.RNA-based vaccines have emerged as a highly effective delivery platform. However, this approach eliminates the possibility for immunogen purification, common in manufacturing of recombinant immunogens. In HIV-1 vaccine design, this is of particular importance because non-native epitopes can compromise the desired immune response, and native immunogen assembly is important for presentation of glycan-based epitopes targeted by broadly neutralizing antibodies. Here, we investigate the assembly and glycosylation of the archetypal trimeric HIV-1 immunogen, BG505, in the soluble single-chain format (NFL.664) that bypasses the need of maturation by furin cleavage. We have investigated the presence of the trimer-associated mannose-patch as oligomannose-type structures at these <i>N</i>-linked glyc2026-01-01T00:00:00Z2026 Jan2026-06-18T05:51:47.303Z2026-06-18T03:07:12.735ZS-EPMC128536484162352410.1039/d5cb00165j