Evaluation of cross-reactivity between anti-PspA antibodies and the S2 subfragment of human cardiac myosin

• Grant number: 12/22250-6
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: February 01, 2013
• End date: November 30, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Luciana Cezar de Cerqueira Leite
• Grantee: Marcela Yumi Wada
• Host Institution: Instituto Butantan. Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 08/05207-4 - Pneumococcal conjugate vaccine: capsular polysaccharide - pneumococcal surface protein A, AP.TEM

Abstract

Pneumococcal surface protein A (PspA) is one of the most protective vaccine antigens against pneumococco in animal models. Thus, its use as a carrier in a polyssacharide conjugate vaccine would be a good strategy to increase the protection and coverage of conjugate vaccines. However, there are reports that anti-PspA antibodies present cross-reactivity with human cardiac myosin. This led to uncertainty about the safety involved in using this protein as a vaccine antigen, since such antibodies could induce cardiac autoimmune disorders, in a similar way to that observed for the M protein of Streptococcus pyogenes. The absence of clinical evidence indicating a relationship between pneumococcal infections and cardiac injuries, argues that this cross-reactivity does not cause a pathological event. Thus, our study aims to investigate this question through two models. In the first model, anti-PspA antibodies will be purified from the serum of healthy individuals. Subsequently, the reactivity profile of these antibodies to cardiac myosin portions (peptides from subfragment S2) will be analyzed and compared with the reactivity profile of sera from patients with rheumatic fever. In the second model, sera from mice colonized with S. pneumoniae or immunized with the recombinant PspA protein will be analyzed for the presence of anti-PspA antibodies and their cross-reactivity with the peptides of cardiac myosin subfragment S2. (AU)