Surface immunogenic protein of streptococcus group b is an agonist of toll-like receptors 2 and 4 and a potential immune adjuvant

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, Flavio Carrión, Magdalena S. Pizarro-Ortega, Christian A.M. Wilson, JULIO ANDRES BERRIOS ARAYA, Alexis M. Kalergis, Abel E. Vasquez

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish
Article number29
JournalVaccines
Volume8
Issue number1
DOIs
StatePublished - Mar 2020
Externally publishedYes

Keywords

  • Adjuvant protein
  • Group B Streptococcus
  • Surface immunogenic protein
  • TRL2 and TLR4 agonist

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