In addition, it is interesting to note that transgenic mice bearing the HLA-DR molecules were more responsive than those bearing the second HLA class II molecules (DQ6 or DQ8). In agreement with these data the IgG specific responses in DR2 and DR4 transgenic mice were slightly better than in

mice bearing DQ6 and DQ8 molecules. Although some mice became nonresponsive a year after the immunization, the immune responses to StreptInCor were maintained for up to a year. These results SB203580 mouse also indicated that the vaccine epitope is able to induce a long period of specific immune responses, with IgG1 predominance due to the effects of the adjuvant. The balance between humoral and cellular immune responses induced by adjuvant formulations can be addressed through the isotype profile of the vaccine-specific IgG1 and IgG2a antibodies produced. The IgG1 isotype switch is dependent of IL-4 production in opposite to isotype IgG2a, which is IFN-γ dependent. We observed a huge predominance of specific IgG1 when compared to IgG2a and also to IgG3, another IFN-γ dependent isotype. It is interesting to note that some IgG2b, a TGF-β-depending switch,

was seen in some animals from all groups studied (DR2, DR4, DQ6 and DQ8). Finally, aluminum PD0332991 research buy adjuvants are responsible for Th2 polarization, resulting in increased humoral immunity, mediated by production of IgG1 isotype. Considering pharyngitis is among the most common S. pyogenes infections, the induction of mucosal immune responses, mainly by IgA secretions, is attractive. Accordingly, other adjuvants are being assayed to obtain both systemic and mucosal immune responses.

One of the major challenges only of producing a vaccine against to S. pyogenes is to not induce autoimmune responses and diseases such as RF and RHD. Although we know the mechanisms that lead the disease in humans [13], there have been no ideal in vivo models of the disease, except for in the Lewis rat [33], until our current study. As myosin is a putative auto-antigen involved in RHD development [33], [34], [35], [36], [37], [38] and [39], we used both human myocardium-derived proteins and porcine cardiac myosin to evaluate the presence of cross-reactive antibodies that could be triggered by the immunizations. No specific cross reactivity against heart proteins was observed indicating that StreptInCor did not induce autoimmune reactions. Myosin heavy chains have been categorized into several classes based on comparisons and phylogenetic analysis of the conserved regions [40], [41] and [42].