Bacterial Lipoprotein (BLP) as Vaccine Adjuvant

Subunit vaccines are relatively less cost to produce by recombinant DNA technology comparing with other types. However, these vaccine candidates usually require adjuvants because of their poor immunogenic. Bacterial lipoproteins are excellent carriers for hapten-conjugates and builtin adjuvant in novel subunit vaccines development. Creative Biolabs is a leader in the field of vaccine development and the extensive experience and expertise of our scientists enable us to provide development services related to innate immune stimulators, particularly the adjuvant development of bacterial lipoprotein.

Bacterial Lipoprotein (BLP)

Toll-like receptors (TLRs) are widely used to regulate innate and adaptive immune responses to antigens and subunit vaccines using TLR agonist has become a hot field of vaccine research and development. Bacterial lipoproteins defined as bacterial proteins are post-translationally modified at the SH group of the N-terminal cysteine residue, wherein the acylglycerol groups are linked by a thioether bond and the amino group is acylated with a fatty acid. Recognized as a danger signal by the immune system, the cysteine-linked diacyl lipid portion of BLP is capable of inducing antimicrobial activity and triggering host defense mechanisms through TLR stimulation. Bacterial lipoprotein has a conserved liposome motif of four amino acids: [LVI][ASTVI][GAS][C]. It is located in the C-terminal part of its leader peptide and contains a conserved cysteine residue which is the target of N-acyl-S-diacylglyceryl-cysteinyl modification.

OspA of Borrelia burgdorferi is the first recombinant bacterial lipoprotein licensed as a vaccine against Lyme disease. Animal immunogenicity studies have shown that lipidated OspA triggers protection against B. burgdorferi challenge. E. coli expressed bivalent recombinant LP2086 is the second recombinant lipoprotein licensed for use in human vaccines. Natural BLP was identified as a human factor H binding protein and was licensed for human vaccine against human meningococcal group B infection.

Schematic structure of recombinant bacterial lipoproteins.

Fig.1 Schematic structure of recombinant bacterial lipoproteins. (Leng CH. 2015)

Synthetic Lipopeptide (Pam3CSK4) as an Adjuvant for Vaccine Formulation

Synthetic bacterial lipopeptide Pam3-Cys-Ser-Lys4 (Pam3CSK4) is a synthetic tripalmitoylated bacterial lipopeptide that mimics the acylated amino terminus of bacterial LPs. It is a potent activator of the proinflammatory transcription factor NF-kB pathway, by forming an m-shaped heterodimer of TLR1 and TLR2 and has been widely used as a vaccine adjuvant to enhance immune responses. The cationic properties and the N-palmitoylated cysteine in Pam3CSK4 as crucial characteristics for enhancement of virus infection.

Creative Biolabs is specialized in assisting clients with every stage of the vaccine development services, including adjuvant optimization. As an innovative and truly premier drug discovery and development research partner, Creative Biolabs is committed to providing the best quality services and high level of specialized support.

Reference

  1. Leng CH, et al. Recombinant bacterial lipoproteins as vaccine candidates. Expert Rev Vaccines. 2015, 14(12): 1623-32.

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