Surface Immunogenic Protein of <i>Streptococcus</i> 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 Berrios,
Alexis M. Kalergis,
Abel E. Vasquez
Affiliations
Diego A. Diaz-Dinamarca
Seccion de Biotecnologia, Instituto de Salud Publica de Chile, Santiago 7780050, Chile
Ricardo A. Manzo
Seccion de Biotecnologia, Instituto de Salud Publica de Chile, Santiago 7780050, Chile
Daniel A. Soto
Seccion de Biotecnologia, Instituto de Salud Publica de Chile, Santiago 7780050, Chile
María José Avendaño-Valenzuela
Seccion de Biotecnologia, Instituto de Salud Publica de Chile, Santiago 7780050, Chile
Diego N. Bastias
Seccion de Biotecnologia, Instituto de Salud Publica de Chile, Santiago 7780050, Chile
Paulina I. Soto
Seccion de Biotecnologia, Instituto de Salud Publica de Chile, Santiago 7780050, Chile
Daniel F. Escobar
Seccion de Biotecnologia, Instituto de Salud Publica de Chile, Santiago 7780050, Chile
Valeria Vasquez-Saez
Seccion de Biotecnologia, Instituto de Salud Publica de Chile, Santiago 7780050, Chile
Flavio Carrión
Programa de Inmunología Traslacional, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Santiago 8320000, Chile
Magdalena S. Pizarro-Ortega
Millenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile
Christian A. M. Wilson
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago 8320000, Chile
Julio Berrios
Escuela de Ingeniería en Bioquímica, Pontificia Universidad Católica de Valparaíso, Valparaíso 2340000, Chile
Alexis M. Kalergis
Millenium Institute on Immunology and Immunotherapy, Departamento de Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8320000, Chile
Abel E. Vasquez
Seccion de Biotecnologia, Instituto de Salud Publica de Chile, Santiago 7780050, Chile
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.