tetano
Editor, Senior Moderator
Int J Biol Macromol
. 2024 May 10:132258.
doi: 10.1016/j.ijbiomac.2024.132258. Online ahead of print. The synthesis and preliminary immunological evaluation of a dual-adjuvant SARS-CoV-2 RBD vaccine: Covalent integration of TLR7/8 and iNKT cell agonists
Ying Xu[SUP] 1 [/SUP], Jing Yang[SUP] 1 [/SUP], Xiongyan Meng[SUP] 1 [/SUP], Shuai Meng[SUP] 1 [/SUP], Tiantian Sun[SUP] 2 [/SUP], Ning Ding[SUP] 3 [/SUP], Chengli Zong[SUP] 4 [/SUP]
Affiliations
Covalently linking an adjuvant to an antigenic protein enhances its immunogenicity by ensuring a synergistic delivery to the immune system, fostering a more robust and targeted immune response. Most adjuvant-protein conjugate vaccines incorporate only one adjuvant due to the difficulties in its synthesis. However, there is a growing interest in developing vaccines with multiple adjuvants designed to elicit a more robust and targeted immune response by engaging different aspects of the immune system for complex diseases where traditional vaccines fall short. Here, we pioneer the synthesis of a dual-adjuvants protein conjugate Vaccine 1 by assembling a toll-like receptor 7/8 (TLR7/8) agonist, an invariant natural killer T cell (iNKT) agonist with a clickable bicyclononyne (BCN). The BCN group can bio-orthogonally react with azide-modified severe acute respiratory syndrome coronavirus-2 receptor-binding domain (SARS-CoV-2 RBD) trimer antigen to give the three-component Vaccine 1. Notably, with a mere 3 μg antigen, it elicited a balanced subclass of IgG titers and 20-fold more IgG2a than control vaccines, highlighting its potential for enhancing antibody-dependent cellular cytotoxicity. This strategy provides a practicable way to synthesize covalently linked dual immunostimulants. It expands the fully synthetic self-adjuvant protein vaccine that uses a single adjuvant to include two different types of adjuvants.
Keywords: Click chemistry; Protein conjugate; Vaccine synthesis.
. 2024 May 10:132258.
doi: 10.1016/j.ijbiomac.2024.132258. Online ahead of print. The synthesis and preliminary immunological evaluation of a dual-adjuvant SARS-CoV-2 RBD vaccine: Covalent integration of TLR7/8 and iNKT cell agonists
Ying Xu[SUP] 1 [/SUP], Jing Yang[SUP] 1 [/SUP], Xiongyan Meng[SUP] 1 [/SUP], Shuai Meng[SUP] 1 [/SUP], Tiantian Sun[SUP] 2 [/SUP], Ning Ding[SUP] 3 [/SUP], Chengli Zong[SUP] 4 [/SUP]
Affiliations
- PMID: 38735613
- DOI: 10.1016/j.ijbiomac.2024.132258
Covalently linking an adjuvant to an antigenic protein enhances its immunogenicity by ensuring a synergistic delivery to the immune system, fostering a more robust and targeted immune response. Most adjuvant-protein conjugate vaccines incorporate only one adjuvant due to the difficulties in its synthesis. However, there is a growing interest in developing vaccines with multiple adjuvants designed to elicit a more robust and targeted immune response by engaging different aspects of the immune system for complex diseases where traditional vaccines fall short. Here, we pioneer the synthesis of a dual-adjuvants protein conjugate Vaccine 1 by assembling a toll-like receptor 7/8 (TLR7/8) agonist, an invariant natural killer T cell (iNKT) agonist with a clickable bicyclononyne (BCN). The BCN group can bio-orthogonally react with azide-modified severe acute respiratory syndrome coronavirus-2 receptor-binding domain (SARS-CoV-2 RBD) trimer antigen to give the three-component Vaccine 1. Notably, with a mere 3 μg antigen, it elicited a balanced subclass of IgG titers and 20-fold more IgG2a than control vaccines, highlighting its potential for enhancing antibody-dependent cellular cytotoxicity. This strategy provides a practicable way to synthesize covalently linked dual immunostimulants. It expands the fully synthetic self-adjuvant protein vaccine that uses a single adjuvant to include two different types of adjuvants.
Keywords: Click chemistry; Protein conjugate; Vaccine synthesis.