Comprehensive Vaccine Design for Commensal Disease Progression

Commensal organisms with the potential to cause disease pose a challenge in

developing treatment options. Using the example featured in this study, pneumococcal disease

begins with Streptococcus pneumoniae colonization followed by triggering events that prompt

release of a virulent sub-population of bacteria. Current vaccines focus upon colonization

prevention, which poses unintended consequences of serotype niche replacement. In the

enclosed work, non-covalent co-localization of two classes of complementary antigens, one to

prevent colonization of the most aggressive S. pneumoniae serotypes and another to restrict

virulence transition, provides complete vaccine effectiveness in animal subjects and the most

comprehensive coverage of disease reported to date. As a result, the proposed vaccine

formulation offers universal pneumococcal disease prevention with the prospect of effectively

managing a disease that afflicts 10s-100s of millions globally. The approach more generally puts

forth a balanced prophylactic treatment strategy in response to complex commensal-host

dynamics.