2. Academic Validation
  3. Simplified scalable synthesis of a water-soluble toll-like receptor 2 agonistic lipopeptide adjuvant for use with protein-based viral vaccines

Simplified scalable synthesis of a water-soluble toll-like receptor 2 agonistic lipopeptide adjuvant for use with protein-based viral vaccines

  • Bioorg Chem. 2024 Sep 22:153:107835. doi: 10.1016/j.bioorg.2024.107835.
Deshkanwar S Brar 1,  Arshpreet Kaur 2,  Madhuri T Patil 3,  Yoshikazu Honda-Okubo 4,  Nikolai Petrovsky 5,  Deepak B Salunke 6
Affiliations

Affiliations

  • 1 Department of Chemistry and Centre of Advanced Studies in Chemistry, Panjab University, Chandigarh 160014, India; National Interdisciplinary Centre of Vaccine Immunotherapeutics and Antimicrobials, Panjab University, Chandigarh 160014, India.
  • 2 Department of Chemistry and Centre of Advanced Studies in Chemistry, Panjab University, Chandigarh 160014, India.
  • 3 Department of Chemistry, Mehr Chand Mahajan DAV College for Women, Chandigarh 160036, India.
  • 4 Vaxine Pty Ltd, 11 Walkley Avenue, Warradale, South Australia 5046, Australia; Australian Respiratory and Sleep Medicine Institute, Bedford Park, South Australia 5042, Australia.
  • 5 Vaxine Pty Ltd, 11 Walkley Avenue, Warradale, South Australia 5046, Australia; Australian Respiratory and Sleep Medicine Institute, Bedford Park, South Australia 5042, Australia; National Interdisciplinary Centre of Vaccine Immunotherapeutics and Antimicrobials, Panjab University, Chandigarh 160014, India. Electronic address: nikolai.petrovsky@vaxine.net.
  • 6 Department of Chemistry and Centre of Advanced Studies in Chemistry, Panjab University, Chandigarh 160014, India; National Interdisciplinary Centre of Vaccine Immunotherapeutics and Antimicrobials, Panjab University, Chandigarh 160014, India. Electronic address: salunke@pu.ac.in.
PMID: 39342891 DOI: 10.1016/j.bioorg.2024.107835
Abstract

Toll-like receptors (TLRs) form a key bridge between the innate and adaptive immune systems. The Lipopeptide based TLR2 agonists such as Pam2CSK4 are promising vaccine adjuvants but drawbacks include its surfactant like nature and cumbersome synthesis. Although the TLR2 activity of Pam2CS-OMe is commensurate with Pam2CSK4, its water solubility is much less, rendering it ineffective for clinical use. In the present investigation, we designed a synthesis pathway for a novel water-soluble TLR2-active analogue, Pam2CS-DMAPA (13), which enhanced the immunogenicity of recombinant SARS-CoV2 and hepatitis B antigens in mice. Co-formulation of compound 13 with 2 % aluminium hydroxide gel led to a further significant improvement in vaccine immunogenicity. This synthetically simpler compound 13 was water soluble and equally potent to Pam2CSK4 Adjuvant, but was superior in terms of manufacturing simplicity and scalability. This makes compound 13 a promising TLR2 targeted Adjuvant for further development.

Keywords

Adjuvant; COVID-19; Lipopeptide; Pam(2)CSK(4); TLR2; Vaccine.

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