Self-Assembled TLR7/8 Agonist-Mannose Conjugate as An Effective Vaccine Adjuvant for SARS-CoV-2 RBD Trimer

Abstract

Small synthetic TLR7/8-agonists can be used as vaccine adjuvants to enhance cell and humoral-mediated immune responses to specific antigens. Despite their potency, after local injection they can be dispersed to undesired body parts causing high reactogenicity, limiting their clinical applications. Here we describe a vaccination strategy that employs the covalent conjugate of a mannose and TLR7/8 agonist as a vaccine adjuvant to take advantage of mannose binding C-type lectins on dendritic cells to enhance the vaccine’s immunogenicity. The mannose-TLR7/8 agonist conjugate can self-assemble into nanoparticles with the hydrophilic mannose on the outside and hydrophobic TLR7/8 agonist inside. Although its ability to stimulate HEK-BlueTM hTLR7/8 cells dropped, it can efficiently stimulate mouse bone marrow-derived dendritic cells as indicated by the up-regulation of CD80 and CD86, and higher cytokine expression levels of TNF-α, IL6, and IL-12p70 than the native TLR7/8 agonist. In vivo, vaccination using the SARS-CoV-2 RBD trimer as the antigen and the conjugate as the adjuvant induced a significantly higher amount of IgG2a. These results suggest that the mannose-TLR7/8-agonist conjugate can be used as an effective vaccine adjuvant.

The Application of Biomaterials for the Vaccine, Treatment, and Detection of SARS-CoV-2

“…In addition, a mannose-TLR7/8 agonist adjuvant could enhance vaccine-induced humoral and cellular immune responses. 30 Chitosan is a promising adjuvant for the COVID-19 vaccines. For instance, Tatlow et al developed an inhaled chitosan-coated DNA vaccine and demonstrated its potential as a preventive COVID-19 vaccine.…”

“…Chitosan can induce inflammasome and promote cellular and humoral immunity by binding to cell surface receptors such as Toll-like receptor-2 (TLR-2) and stimulating the DNA sensor cGAS-STING pathway to induce dendritic cell (DC) maturation and TH1 immune response in type I interferons. In addition, a mannose-TLR7/8 agonist adjuvant could enhance vaccine-induced humoral and cellular immune responses …”

“…In addition, a mannose-TLR7/8 agonist adjuvant could enhance vaccine-induced humoral and cellular immune responses. 30 …”