ArticleHeliyon2023
Physicochemical characterization of biological and synthetic forms of two lipid A-based TLR4 agonists.
Article in Heliyon, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 14 citations in OpenAlex.
- A multivalent subunit vaccine augments pre-existing immunity to protect against T3SS-positiveInfection and immunity · 2026Article
- Optimizing an avian influenza vaccine using a novel Bacterial Enzymatic Combinatorial Chemistry (BECC) TLR4 adjuvant.mSphere · 2026Article
- Eco-tank Housing Maintains Wild-Type Microbiota and Rewilds the Laboratory Mouse Gut Microbiome to Restore Natural Immune Tone.bioRxiv : the preprint server for biology · 2026Article
- Comparative immunogenicity and protective efficacy of BECC438 and BECC470 adjuvants in a vaccine formulation againstFrontiers in immunology · 2026Article
- Risk of autoimmune disease flares after recombinant zoster vaccine: A vaccine safety analysis based on the Vaccine Adverse Event Reporting System database.Human vaccines & immunotherapeutics · 2025Article
- A high-throughput multi-species platform using Biolayer Interferometry Immunosorbent Assay (BLI-ISA) as an alternative to indirect ELISA for vaccine development.Journal of immunological methods · 2025Article
- Innovative design and comprehensive characterization of a valine-enhanced lipid nanoparticle-coated mRNA vaccine targeting the SARS-CoV-2 S-RBD antigen.Scientific reports · 2025Article
- Lipid A mimetic BECC438 potentiates durable and balanced antibody responses in an ovalbumin murine model of vaccination.ImmunoHorizons · 2025Article
- Review
- Immune profile diversity is achieved with synthetic TLR4 agonists combined with the RG1-VLP vaccine in mice.Vaccine · 2025Article
- Diversity, Complexity, and Specificity of Bacterial Lipopolysaccharide (LPS) Structures Impacting Their Detection and Quantification.International journal of molecular sciences · 2024Article
- Advances in protein subunit vaccines against H1N1/09 influenza.Frontiers in immunology · 2024Review
- Development of a nano-emulsion based multivalent protein subunit vaccine againstFrontiers in immunology · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor (TLR) agonists are recognized as potential immune-enhancing adjuvants and are included in several licensed vaccines. Monophosphoryl lipid A (MPL®, GlaxoSmithKline) is one such TLR4 agonist that has been approved for use in human vaccines, such as Cervarix and Shingrix. Due to the heterogeneous nature of biologically derived MPL and the need for safer and more potent adjuvants, our groups have developed the novel TLR4 agonist candidates, BECC438 and BECC470 using the Bacterial Enzymatic Combinatorial Chemistry (BECC) platform. BECC438 and BECC470 have been included in studies to test their adjuvant potential and found to be effective in vaccines against both viral and bacterial disease agents. Here, we report detailed biophysical characterization of BECC438 and BECC470 purified from a biological source (BECC438b and BECC470b, respectively) and synthesized chemically (BECC438s and BECC470s, respectively). Both BECC438s and BECC470s have identical acyl chain configurations, BECC438s is bis-phosphorylated and BECC470s is mono-phosphorylated with the removal of the 4' phosphate moiety. We determined the phase transition temperatures for the acyl chains of BECC438b and BECC470b and found them to be different from those exhibited by their synthetic counterparts. Furthermore, the phosphate groups of BECC438b and BECC470b are more highly hydrated than are those of BECC438s and BECC470s. In addition to exploring the BECC molecules' biophysical features in aqueous solution, we explored potential formulation of BECC438 and BECC470 with the aluminum-based adjuvant Alhydrogel and as part of an oil-in-water emulsion (Medimmune Emulsion or ME). All of the lipid A analogues could be fully absorbed to Alhydrogel or incorporated onto ME. Surprisingly, the BECC470s molecule, unlike the others, displayed a nearly baseline signal when monitored using a Limulus amebocyte lysate (LAL) endotoxin detection system. Despite this, it was shown to behave as an agonist for human and mouse TLR4 when tested using multiple cell-based systems. This work paves the way for further formulation optimization of two chemically defined TLR4 agonists that are showing great promise as vaccine adjuvants.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.