Abstract
Vaccine-induced protection against pathogens, especially subunit-based vaccines, are related to antigen properties but mainly in their ability to stimulate the immune system by the use of an adjuvant. Modern vaccines are formulated with a high level of antigen purity, where an efficient adjuvant is necessary. In this context, the use of protein Toll-Like Receptor (TLR) agonists as vaccine adjuvants has been highlighted because of their optimal immunogenicity and minimal toxicity. The Surface Immunogenic Protein (SIP) from Group B Streptococcus (GBS) has gained importance as a new potential protein-based vaccine. Recently, we reported that recombinant SIP (rSIP) expressed by E. coli and purified by High Performance Liquid Chromatography (HPLC) alone induces a protective humoral immune response. In this study, we present the immunomodulatory properties of rSIP as a protein-based adjuvant, as an agonist of TLR. To this end, we showed that C57BL/6 bone marrow-derived dendritic cells pulsed by rSIP resulted in enhanced CD40, CD80, CD86, and Major Histocompatibility Complex (MHC) class II as well as increased secretion proinflammatory cytokines Interleukin (IL)-6, Interferon (IFN)-γ, Tumor Necrosis Factor (TNF)-α, and IL-10. Next, we investigated the in vivo effect of rSIP in the absence or presence of ovalbumin (OVA) on antigen-specific antibody secretion in C57BL/6 mice. Immunization with rSIP plus OVA showed that anti-OVA IgG2a and IgG1a increased significantly compared with OVA alone in C57BL/6 mice. Also, the immunization of rSIP plus OVA generates increased serum cytokines levels characterized by IL-12p70, IL-10, IL-4, and IFN-γ. Interestingly, we observed that rSIP stimulate Toll Like Receptor (TLR)2 and TLR4, individually expressed by Human embryonic kidney (HEK) 293-derived TLR reporter cells. These findings suggest that rSIP is a new potential protein TLR agonist adjuvant and may be employed in the development of new vaccines.
Highlights
The majority of new human vaccines are based on purified antigens, which generally have low immunogenicity, and adjuvants are necessary to improve vaccine-induced immune responses [1,2].Due to their role in self/nonself-differentiation and their ability to induce professional antigen-presenting cell (APC) maturation and to subsequently trigger stronger immune responses, Toll-Like Receptor (TLR) agonists are considered promising adjuvant candidates [2,3]
We showed that C57BL/6 bone marrow-derived dendritic cells (DCs) (BM-DC) stimulated with recombinant SIP (rSIP) resulted in enhanced co-stimulatory proteins as well as enhanced production of proinflammatory cytokines IL-6, IFN-γ, Tumor Necrosis Factor (TNF)-α, and IL-10
The results showed that rSIP promotes the production of proinflammatory cytokines from BM-DCs results showed that rSIP promotes the production of proinflammatory cytokines from BM-DCs at at both concentrations of 1 μg/mL and 10 μg/mL
Summary
The majority of new human vaccines are based on purified antigens, which generally have low immunogenicity, and adjuvants are necessary to improve vaccine-induced immune responses [1,2] Due to their role in self/nonself-differentiation and their ability to induce professional antigen-presenting cell (APC) maturation and to subsequently trigger stronger immune responses, Toll-Like Receptor (TLR) agonists are considered promising adjuvant candidates [2,3]. In this regard, the majority of the currently investigated TLR agonists are nonprotein microbial components such as lipopolysaccharides, oligonucleotides, and lipopeptides [4]. Protein adjuvants can be genetically fused to protein antigens, ensuring the co-delivery of adjuvant antigens, leading to more effective activation of the innate and adaptive immune responses [3,4].
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