Abstract
Streptococcus pyogenes infection continues to be a worldwide public health problem causing various diseases in humans and plays an important role in the pathogenesis of rheumatic fever and rheumatic heart disease. We developed a vaccine candidate to prevent S. pyogenes infections, identified as StreptInCor, that presented promising results in mouse models. A certified and independent laboratory conducted two repeated intramuscular dose toxicity tests (28 days, four weekly injections). The first test, composed of four experimental groups treated with 0 (vehicle), 50, 100 or 200 µg/500 µL StreptInCor, did not show significant alterations in clinical, hematological, biochemical or anatomopathological parameters related to the administration of StreptInCor. In addition to the parameters mentioned above, we evaluated the cardiac function and valves of animals by echocardiography before and after administration of 200 µg/500 µL StreptInCor versus placebo. We did not observe any changes related to StreptInCor administration, including changes in cardiac function and valves in animals, after receiving the highest dose of this vaccine candidate. The results obtained in the two repeated intramuscular dose toxicity tests showed that this vaccine formulation did not induce harmful effects to the tissues and organs studied, indicating that the candidate vaccine is well tolerated in minipigs.
Highlights
RF and RHD begins in childhood, usually in children living in poor health and housing conditions, associated with poverty, which facilitates the emergence of recurrent infections by GAS
Streptococcal M protein is the major surface protein and the more antigenic antigen. It is composed of two α-helix polypeptide chains anchored in the S. pyogenes cell wall and is extremely polymorphic and antigenic in its N-terminal region, which defines the different serotypes of GAS and the C-terminal region that is highly conserved among the different serotypes of GAS10
Seven days after the last administration of the formulations we collected blood samples for hematological and biochemical evaluation as well as titration of antibodies produced against StreptInCor
Summary
RF and RHD begins in childhood, usually in children living in poor health and housing conditions, associated with poverty, which facilitates the emergence of recurrent infections by GAS. Several studies show the existence of genes related to RF and RHD susceptibility in the host In this sense, several polymorphisms in genes encoding immunity-related proteins have been described. Aluminum hydroxide-diluted StreptInCor, tested on inbred, outbred and transgenic mice harboring human HLA class II alleles, has been shown to be an excellent immunogen with no cross-reaction with cardiac proteins and no deleterious effects in vaccinated animals[18,19]. Based on these data, an independent laboratory performed and conducted preclinical evaluation in rodent and nonrodent. Two repeated dose experiments in minipigs were performed to verify possible toxic effects as well as signs of heart injuries in response to the administration of our vaccine candidate in these animals
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
