Surface Immunogenic Protein of Streptococcus Group B is an Agonist of Toll-Like Receptors 2 and 4 and a Potential Immune Adjuvant
Journal
Vaccines
ISSN
2076-393X
Date Issued
2020
Author(s)
Diego A. Diaz-Dinamarca
Ricardo A. Manzo
Daniel A. Soto
María José Avendaño-Valenzuela
Diego N. Bastias
Paulina I. Soto
Daniel F. Escobar
Valeria Vasquez-Saez
Magdalena S. Pizarro-Ortega
Christian A. M. Wilson
Julio Berrios
Alexis M. Kalergis
Abel E. Vasquez
Type
Resource Types::text::journal::journal article
URL Institutional Repository
Abstract
<jats:p>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.</jats:p>
Cite this document
Diaz-Dinamarca, D. A., Manzo, R. A., Soto, D. A., Avendaño-Valenzuela, M. J., Bastias, D. N., Soto, P. I., Escobar, D. F., Vasquez-Saez, V., Carrión, F., Pizarro-Ortega, M. S., Wilson, C. A. M., Berrios, J., Kalergis, A. M., & Vasquez, A. E. (2020). Surface immunogenic protein of streptococcus group b is an agonist of toll-like receptors 2 and 4 and a potential immune adjuvant. Vaccines, 8(1), 29. https://doi.org/10.3390/vaccines8010029
Subjects
adjuvant protein
;
group b streptococcus
;
surface immunogenic protein
;
trl2 and tlr4 agonist
;
alkaline phosphatase
;
aluminum potassium sulfate
;
b7 antigen
;
bicinchoninic acid
;
caspase 3
;
cd40 antigen
;
cd86 antigen
;
gamma interferon
;
glycoprotein p 15095
;
i kappa b
;
immunoglobulin g
;
immunoglobulin g1
;
immunoglobulin g2a
;
immunological adjuvant
;
interleukin 10
;
interleukin 12p70
;
interleukin 6
;
major histocompatibility complex class ii
;
ovalbumin
;
surface immunogenic protein
;
toll like receptor 2
;
toll like receptor 4
;
tumor necrosis factor
;
unclassified drug
;
vaccine
;
animal cell
;
animal experiment
;
animal model
;
apoptosis
;
article
;
cd8+ t lymphocyte
;
cell death
;
cell maturation
;
cell viability
;
circular dichroism
;
comparative study
;
controlled study
;
cytokine production
;
cytokine release
;
cytokine response
;
cytotoxicity
;
dendritic cell
;
drug toxicity
;
enzyme immunoassay
;
enzyme linked immunosorbent assay
;
escherichia coli
;
female
;
flow cytometry
;
hek293 cell line
;
high performance liquid chromatography
;
immune response
;
immune system
;
immunization
;
immunogenicity
;
immunotherapy
;
macrophage
;
major histocompatibility complex
;
mouse
;
nonhuman
;
peptide synthesis
;
phenotype
;
protein expression
;
size exclusion chromatography
;
streptococcus agalactiae
;
vaccination
;
western blotting