Antibodies Reactive to Commensal Streptococcus mitis Show Cross-Reactivity With Virulent Streptococcus pneumoniae Serotypes

Abstract

Current vaccines against <i>Streptococcus pneumoniae</i>, a bacterial species that afflicts people by causing a wide spectrum of diseases, do not protect against all pneumococcal serotypes. Thus, alternative vaccines to fight pneumococcal infections that target common proteins are under investigation. One promising strategy is to take advantage of immune cross-reactivity between commensal and pathogenic microbes for cross-protection. In this study, we examined the antibody-mediated cross-reactivity between <i>S. pneumoniae</i> and <i>Streptococcus mitis</i>, a commensal species closely related to <i>S. pneumoniae</i>. Western blot analysis showed that rabbit antisera raised against <i>S. mitis</i> reacted with multiple proteins of virulent <i>S. pneumoniae</i> strains (6B, TIGR4, and D39). Rabbit anti-<i>S. pneumoniae</i> IgG antibodies also showed binding to <i>S. mitis</i> antigens. Incubation of rabbit antisera raised against <i>S. mitis</i> with heterologous or homologous bacterial lysates resulted in marked inhibition of the developments of bands in the Western blots. Furthermore, plasma IgG antibodies from adult human volunteers intranasally inoculated with <i>S. pneumoniae</i> 6B revealed enhanced <i>S. mitis</i>-specific IgG titers compared with the pre-inoculation samples. Using an on-chip protein microarray representing a number of selected membrane and extracellular <i>S. pneumoniae</i> proteins, we identified choline-binding protein D (CbpD), cell division protein (FtsH), and manganese ABC transporter or manganese-binding adhesion lipoprotein (PsaA) as common targets of the rabbit IgG antibodies raised against <i>S. mitis</i> or <i>S. pneumoniae</i>. Cumulatively, these findings provide evidence on the antibody-mediated cross-reactivity of proteins from <i>S. mitis</i> and <i>S. pneumoniae</i>, which may have implications for development of effective and wide-range pneumococcal vaccines.