ArticleVaccine2021
A non-affinity purification process for GMP production of prefusion-closed HIV-1 envelope trimers from clades A and C for clinical evaluation.
Article in Vaccine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Canonical Antibodies Adopt Distinct Binding Modes to Recognize Viral Glycan Shields.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Production of Clinical-Grade SARS-CoV-2 Spike Ferritin Nanoparticle Protein Immunogen by Transient Transfection.Vaccines · 2025Article
- Accelerated cGMP production of near-native HIV-1 Env trimers following electroporation transfection and immunogenicity analysis.NPJ vaccines · 2025Article
- Transient glycan shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques.Cell reports · 2025Article
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- Article
- RAIN: machine learning-based identification for HIV-1 bNAbs.Nature communications · 2024Article
- RAIN: a Machine Learning-based identification for HIV-1 bNAbs.Research square · 2024Article
- Article
- HIV-1 neutralizing antibodies elicited in humans by a prefusion-stabilized envelope trimer form a reproducible class targeting fusion peptide.Cell reports · 2023Article
- Diverse Murine Vaccinations Reveal Distinct Antibody Classes to Target Fusion Peptide and Variation in Peptide Length to Improve HIV Neutralization.Journal of virology · 2023Article
- Assessment of Crosslinkers between Peptide Antigen and Carrier Protein for Fusion Peptide-Directed Vaccines against HIV-1.Vaccines · 2022Article
- Structural basis for llama nanobody recognition and neutralization of HIV-1 at the CD4-binding site.Structure (London, England : 1993) · 2022Article
- Safety and immunogenicity of an HIV-1 prefusion-stabilized envelope trimer (Trimer 4571) vaccine in healthy adults: A first-in-human open-label, randomized, dose-escalation, phase 1 clinical trial.EClinicalMedicine · 2022Article
- Advances in purification of SARS-CoV-2 spike ectodomain protein using high-throughput screening and non-affinity methods.Scientific reports · 2022Article
- Structural basis of glycan276-dependent recognition by HIV-1 broadly neutralizing antibodies.Cell reports · 2021Article
- Advances in Purification of SARS-CoV-2 Spike Ectodomain Protein Using High-Throughput Screening and Non-Affinity Methods.Research square · 2021Article
- Structural Basis of Antibody Conformation and Stability Modulation by Framework Somatic Hypermutation.Frontiers in immunology · 2021Article
- Bispecific antibody CAP256.J3LS targets V2-apex and CD4-binding sites with high breadth and potency.mAbsArticle
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Authors and funding
17 authors.
Funding
Abstract
Metastable glycosylated immunogens present challenges for GMP manufacturing. The HIV-1 envelope (Env) glycoprotein trimer is covered by N-linked glycan comprising half its mass and requires both trimer assembly and subunit cleavage to fold into a prefusion-closed conformation. This conformation, the vaccine-desired antigenic state, is both metastable to structural rearrangement and labile to subunit dissociation. Prior reported GMP manufacturing for a soluble trimer stabilized in a near-native state by disulfide (SOS) and Ile-to-Pro (IP) mutations has employed affinity methods based on antibody 2G12, which recognizes only ~30% of circulating HIV strains. Here, we develop a scalable manufacturing process based on commercially available, non-affinity resins, and we apply the process to current GMP (cGMP) production of trimers from clades A and C, which have been found to boost cross-clade neutralizing responses in vaccine-test species. The clade A trimer, which we named "BG505 DS-SOSIP.664", contained an engineered disulfide (201C-433C; DS) within gp120, which further stabilized this trimer in a prefusion-closed conformation resistant to CD4-induced triggering. BG505 DS-SOSIP.664 was expressed in a CHO-DG44 stable cell line and purified with initial and final tangential flow filtration steps, three commercially available resin-based chromatography steps, and two orthogonal viral clearance steps. The non-affinity purification enabled efficient scale-up, with a 250 L-scale cGMP run yielding 9.6 g of purified BG505 DS-SOSIP.664. Antigenic analysis indicated retention of a prefusion-closed conformation, including recognition by apex-directed and fusion peptide-directed antibodies. The developed manufacturing process was suitable for 50 L-scale production of a second prefusion-stabilized Env trimer vaccine candidate, ConC-FP8v2 RnS-3mut-2G-SOSIP.664, yielding 7.8 g of this consensus clade C trimer. The successful process development and purification scale-up of HIV-1 Env trimers from different clades by using commercially available materials provide experimental demonstration for cGMP manufacturing of trimeric HIV-Env vaccine immunogens, in an antigenically desired conformation, without the use of costly affinity resins.
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