StreptInCor: A Candidate Vaccine Epitope against S. pyogenes Infections Induces Protection in Outbred Mice

Abstract

Infection with Streptococcus pyogenes (S. pyogenes) can result in several diseases, particularly in children. S. pyogenes M protein is the major virulence factor, and certain regions of its N-terminus can trigger autoimmune sequelae such as rheumatic fever in susceptible individuals with untreated group A streptococcal pharyngitis. In a previous study, we utilized a large panel of human peripheral blood cells to define the C-terminal protective epitope StreptInCor (medical identity), which does not induce autoimmune reactions. We recently confirmed the results in HLA-transgenic mice. In the present study, we extended the experimental assays to outbred animals (Swiss mice). Herein, we demonstrate high titers of StreptInCor-specific antibodies, as well as appropriate T-cell immune responses. No cross-reaction to cardiac myosin was detected. Additionally, immunized Swiss mice exhibited 87% survival one month after challenge with S. pyogenes. In conclusion, the data presented herein reinforce previous results in humans and animals and further emphasize that StreptInCor could be an effective and safe vaccine for the prevention of S. pyogenes infections.

Immunopathological and Comparative Study of Concanavalin- A and Streptococcus lyophilized Antigen in Immunized Rats

“…In vitro, streptococcal pyrogenic exotoxin A (SPEA) stimulate murine T-lymphocyte result by serial of varied seen in lymphoid tissues after streptococcal sepsis were consistent with an in vivo superantigen response as well as proinflammatory streptococcal pyrogenic exotoxin A (SPEA) induced responses can provide for protecting innate responses through aggressive sepsis (Donlan, 2001), our result concluded that display to bacterial superantigen in sepsis performed directly to infiltrate lymphoblastic tissues mainly in splenic immunized group and confirmed best correlation between immunological and pathological finding. Subcutaneous immunization with streptococcus antigen accompanied with adjuvant enhancement potential effect of immune response as compared with negative control group and this observation consistence with several authors idea who mentioned that subcutaneous (Edilberto et al, 2013) intramuscular (Tan et al, 2021) and intranasal (Aniela et al, 2018) vaccination with effective adjuvanted protein prevent even fatal invasion infections in mice, but great improvement in immune response reported in mixed immunized group and that may indicate passive transfer of immunity used antisera and collective human immunoglobulin when it's highly concentration successful to induce immunity in animal models (Reglinski et al, 2015). Obvious reduction in the Immunoglobulin G IgG levels were recorded in the streptococcus antigen immunized group as compared with other immunized groups this evidence may be due to regulation activity of streptococcal cysteine protease, Streptococcal pyrogenic exotoxin B Spe B, by cleaving bacterial and host protein also may be explained that Strep A strategic for inhibiting antibody function include specific proteases of Immunoglobulin G IgG, Ides and EndoS, that split antibodies at Fc region (Ulrich et al, 2002).…”

Immunopathological and Comparative Study of Concanavalin- A and Streptococcus lyophilized Antigen in Immunized Rats

“…In vitro, streptococcal pyrogenic exotoxin A (SPEA) stimulate murine T-lymphocyte result by serial of varied seen in lymphoid tissues after streptococcal sepsis were consistent with an in vivo superantigen response as well as proinflammatory streptococcal pyrogenic exotoxin A (SPEA) induced responses can provide for protecting innate responses through aggressive sepsis (Donlan, 2001), our result concluded that display to bacterial superantigen in sepsis performed directly to infiltrate lymphoblastic tissues mainly in splenic immunized group and confirmed best correlation between immunological and pathological finding. Subcutaneous immunization with streptococcus antigen accompanied with adjuvant enhancement potential effect of immune response as compared with negative control group and this observation consistence with several authors idea who mentioned that subcutaneous (Edilberto et al, 2013) intramuscular (Tan et al, 2021) and intranasal (Aniela et al, 2018) vaccination with effective adjuvanted protein prevent even fatal invasion infections in mice, but great improvement in immune response reported in mixed immunized group and that may indicate passive transfer of immunity used antisera and collective human immunoglobulin when it's highly concentration successful to induce immunity in animal models (Reglinski et al, 2015). Obvious reduction in the Immunoglobulin G IgG levels were recorded in the streptococcus antigen immunized group as compared with other immunized groups this evidence may be due to regulation activity of streptococcal cysteine protease, Streptococcal pyrogenic exotoxin B Spe B, by cleaving bacterial and host protein also may be explained that Strep A strategic for inhibiting antibody function include specific proteases of Immunoglobulin G IgG, Ides and EndoS, that split antibodies at Fc region (Ulrich et al, 2002).…”

StreptInCor, a Group A Streptococcal Adsorbed Vaccine: Evaluation of Repeated Intramuscular Dose Toxicity Testing in Rats

“…The C-terminal region that is conserved did not induce cross-reactive antibodies. In this context, in previous studies on isogenic, outbred, and HLA class II-transgenic mice immunized with StreptInCor ( 24 , 25 ), no heart-tissue cross-reactive antibodies or deleterious reactions in the heart (myocardium and valves) or other tissues were observed. The repeated dose toxicity test performed on Wistar rats presented here showed no signs of toxic reaction in the heart or any of the organs evaluated after the administration of the StreptInCor candidate vaccine.…”

GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A Streptococcus

“…Better estimates of the disease will also facilitate further investment and development of a vaccine against GAS [ 44 ]. Thus far, only M protein-based candidate vaccines have been tested in clinical trials [ 45 , 46 , 47 , 48 ], but conserved protein antigens and surface polysaccharides have also been proposed as vaccine candidates in development [ 49 ]. Among them, GAC conjugate represents an attractive alternative vaccine candidate [ 45 ].…”

Immunopathological and Comparative Study of Concanavalin- A and Streptococcus lyophilized Antigen in Immunized Rats

“…In vitro, streptococcal pyrogenic exotoxin A (SPEA) stimulate murine T-lymphocyte result by serial of varied seen in lymphoid tissues after streptococcal sepsis were consistent with an in vivo superantigen response as well as proinflammatory streptococcal pyrogenic exotoxin A (SPEA) induced responses can provide for protecting innate responses through aggressive sepsis (Donlan, 2001), our result concluded that display to bacterial superantigen in sepsis performed directly to infiltrate lymphoblastic tissues mainly in splenic immunized group and confirmed best correlation between immunological and pathological finding. Subcutaneous immunization with streptococcus antigen accompanied with adjuvant enhancement potential effect of immune response as compared with negative control group and this observation consistence with several authors idea who mentioned that subcutaneous (Edilberto et al, 2013) intramuscular (Tan et al, 2021) and intranasal (Aniela et al, 2018) vaccination with effective adjuvanted protein prevent even fatal invasion infections in mice, but great improvement in immune response reported in mixed immunized group and that may indicate passive transfer of immunity used antisera and collective human immunoglobulin when it's highly concentration successful to induce immunity in animal models (Reglinski et al, 2015). Obvious reduction in the Immunoglobulin G IgG levels were recorded in the streptococcus antigen immunized group as compared with other immunized groups this evidence may be due to regulation activity of streptococcal cysteine protease, Streptococcal pyrogenic exotoxin B Spe B, by cleaving bacterial and host protein also may be explained that Strep A strategic for inhibiting antibody function include specific proteases of Immunoglobulin G IgG, Ides and EndoS, that split antibodies at Fc region (Ulrich et al, 2002).…”

StreptInCor, a Group A Streptococcal Adsorbed Vaccine: Evaluation of Repeated Intramuscular Dose Toxicity Testing in Rats

“…The C-terminal region that is conserved did not induce cross-reactive antibodies. In this context, in previous studies on isogenic, outbred, and HLA class II-transgenic mice immunized with StreptInCor ( 24 , 25 ), no heart-tissue cross-reactive antibodies or deleterious reactions in the heart (myocardium and valves) or other tissues were observed. The repeated dose toxicity test performed on Wistar rats presented here showed no signs of toxic reaction in the heart or any of the organs evaluated after the administration of the StreptInCor candidate vaccine.…”

GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A Streptococcus

“…Better estimates of the disease will also facilitate further investment and development of a vaccine against GAS [ 44 ]. Thus far, only M protein-based candidate vaccines have been tested in clinical trials [ 45 , 46 , 47 , 48 ], but conserved protein antigens and surface polysaccharides have also been proposed as vaccine candidates in development [ 49 ]. Among them, GAC conjugate represents an attractive alternative vaccine candidate [ 45 ].…”

Immunopathological and Comparative Study of Concanavalin- A and Streptococcus lyophilized Antigen in Immunized Rats

“…In vitro, streptococcal pyrogenic exotoxin A (SPEA) stimulate murine T-lymphocyte result by serial of varied seen in lymphoid tissues after streptococcal sepsis were consistent with an in vivo superantigen response as well as proinflammatory streptococcal pyrogenic exotoxin A (SPEA) induced responses can provide for protecting innate responses through aggressive sepsis (Donlan, 2001), our result concluded that display to bacterial superantigen in sepsis performed directly to infiltrate lymphoblastic tissues mainly in splenic immunized group and confirmed best correlation between immunological and pathological finding. Subcutaneous immunization with streptococcus antigen accompanied with adjuvant enhancement potential effect of immune response as compared with negative control group and this observation consistence with several authors idea who mentioned that subcutaneous (Edilberto et al, 2013) intramuscular (Tan et al, 2021) and intranasal (Aniela et al, 2018) vaccination with effective adjuvanted protein prevent even fatal invasion infections in mice, but great improvement in immune response reported in mixed immunized group and that may indicate passive transfer of immunity used antisera and collective human immunoglobulin when it's highly concentration successful to induce immunity in animal models (Reglinski et al, 2015). Obvious reduction in the Immunoglobulin G IgG levels were recorded in the streptococcus antigen immunized group as compared with other immunized groups this evidence may be due to regulation activity of streptococcal cysteine protease, Streptococcal pyrogenic exotoxin B Spe B, by cleaving bacterial and host protein also may be explained that Strep A strategic for inhibiting antibody function include specific proteases of Immunoglobulin G IgG, Ides and EndoS, that split antibodies at Fc region (Ulrich et al, 2002).…”

StreptInCor, a Group A Streptococcal Adsorbed Vaccine: Evaluation of Repeated Intramuscular Dose Toxicity Testing in Rats

“…The C-terminal region that is conserved did not induce cross-reactive antibodies. In this context, in previous studies on isogenic, outbred, and HLA class II-transgenic mice immunized with StreptInCor ( 24 , 25 ), no heart-tissue cross-reactive antibodies or deleterious reactions in the heart (myocardium and valves) or other tissues were observed. The repeated dose toxicity test performed on Wistar rats presented here showed no signs of toxic reaction in the heart or any of the organs evaluated after the administration of the StreptInCor candidate vaccine.…”

GMMA as an Alternative Carrier for a Glycoconjugate Vaccine against Group A Streptococcus

“…Better estimates of the disease will also facilitate further investment and development of a vaccine against GAS [ 44 ]. Thus far, only M protein-based candidate vaccines have been tested in clinical trials [ 45 , 46 , 47 , 48 ], but conserved protein antigens and surface polysaccharides have also been proposed as vaccine candidates in development [ 49 ]. Among them, GAC conjugate represents an attractive alternative vaccine candidate [ 45 ].…”