Construction and Activity Study of β-1,4-GlcNAc Modified Wall Teichoic Acid Conjugate Vaccine by Endogenous Antibody Targeted Synergistic Strategy

• 1、School of Biological Engineering,Jiangnan University,214122

Abstract：Wall teichoic acid (WTA) is the main component of the extracellular membrane of Staphylococcus aureus and is composed of polyribitol phosphate (RboP) glycosylated by α/β-GlcNAc. WTA is a potential target for vaccine design, but it has weak immunogenicity and is difficult to activate an effective immune response. The endogenous antibody recruitment immunomodulation strategy can effectively enhance the efficiency of vaccines. It utilizes naturally existing antibodies in the body (such as anti-rhamnose (Rha) antibodies) to target antigen-presenting cells, thereby promoting antigen delivery and enhancing the immune response. This thesis synthesized the monomer RboP antigen (RP4β) modified by β-1,4-GlcNAc, coupled with bovine serum albumin (BSA) and tetanus toxoid (TT), and modified the Rha semi-antigen on the vaccine molecules for endogenous antibody recruitment, constructing the RP4β-BSA-Rha and RP4β-TT-Rha vaccines. The immunogenicity of the vaccines was systematically evaluated through cell experiments and in vivo immune experiments in mice. The immunogenicity evaluation results showed that the TT carrier protein demonstrated significant immune superiority, and the Rha-modified vaccine could induce higher titers of specific antibodies. The serum antibodies against methicillin-sensitive/more resistant strains had an in vitro clearance rate of 88.3% ± 3.8%. This study successfully constructed an endogenous antibody recruitment immunomodulation type vaccine for methicillin-resistant Staphylococcus aureus, providing an innovative technical path for the development of vaccines against methicillin-resistant Staphylococcus aureus.

Keywords： Staphylococcus aureus Wall teichoic acid Rhamnose Glycoprotein conjugates Vaccines.