StreptInCor: a candidate vaccine epitope against S. pyogenes infections induces protection in outbred mice.

PLoS One. 2013 Apr 8;8(4):e60969.

Postol E, Alencar R, Higa FT, Freschi de Barros S, Demarchi LM, Kalil J, Guilherme L.

Heart Institute, School of Medicine, University of São Paulo, São Paulo, Brazil.

 

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.

PMID: 23593359

 

Supplements:

StreptInCor, the vaccine candidate, presents a unique molecular folding composed of two disordered micro domains corresponding to the T and B epitopes, linked by an 18-amino-acid α-helix as defined by Nuclear Magnetic Resonance spectroscopy (NMR). Since it is a long peptide, antigen processing by antigen presenting cells (i.e., macrophages, dendritic cells and B lymphocytes) is fundamental for both T and B cell recognition. In addition, the amino acid sequences generated by antigen processing are suitable for binding to different HLA-class II molecules, rendering a universal immune response (Guilherme et al, J Biol Chem, 2011).

Luiza Guilherme

Figure 1: Three dimentional molecular structure of StreptInCor peptide, a candidate vaccine against S. pyogenes

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