Poster Presentation 20th Lancefield International Symposium on Streptococci and Streptococcal Diseases 2017

Toxicity and skin sensitization assays as preclinical evaluations of StreptInCor a candidate vaccine to prevent S. pyogenes infections (#166)

Edilberto Postol 1 2 , Luiz Carlos Sa-Rocha 2 3 , Raquel Alencar 1 2 , Jorge Kalil 1 2 4 , Luiza Guilherme 1 2
  1. Heart Institute (InCor), School of Medicine, University of São Paulo, São Paulo, Brazil
  2. Institute for Immunology Investigation, National Institute for Science and Technology, São Paulo, Brazil
  3. Neuroimmunology Laboratory, School of Veterinary Medicine and Animal Sciences, University of São Paulo, São Paulo, Brazil
  4. Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, São Paulo, Brazil

Aiming the development of a vaccine to prevent Streptococcus pyogenes infection and autoimmune disorders we analyzed a large panel of sera and T cells from human blood against 79 overlapping C-terminal synthetic peptides that allowed us to define both T and B epitopes with potential to induce protective immune response. Through this approach, we constructed by chemical synthesis a 55 mers peptide identified as StreptInCor, a candidate vaccine. We tested the ability of StreptInCor to induce protective antibodies by immunizing inbred (BALB/c), outbred (Swiss) and HLA class II (DR2, DR4, DQ6 and DQ8) transgenic mice. Our results showed strong humoral as well as cellular immune responses. To assess the safety of the candidate vaccine, three formulations were prepared under good manufacturing practice conditions: 50, 100 and 200 μg/500 μL of StreptInCor and placebo, onto aluminum hydroxide. These studies were performed by a certified and independent company (Tecam Laboratórios). The vaccine formulations were evaluated in animals for acute and repeated dose toxicity (Wistar rats) and local tolerance (Dunkin-Hartley guinea pigs). Toxicological studies showed that StreptInCor did not induce toxicity. Furthermore, StreptInCor was classified as non-sensitizing to the skin of guinea pigs.

Financial Support: Conselho Nacional de Desenvolvimento e Pesquisa (CNPq), Banco Nacional de Desenvolvimento Econômico e Social (BNDES), Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (INCT-iii)