학술논문

Directed vaccination against pneumococcal disease
Document Type
Source
Proceedings of the National Academy of Sciences. 113(25):6898-6903
Subject
Medicin och hälsovetenskap
Medicinska och farmaceutiska grundvetenskaper
Immunologi inom det medicinska området
Medical and Health Sciences
Basic Medicine
Immunology in the medical area
Language
English
ISSN
1091-6490
Abstract
Immunization strategies against commensal bacterial pathogens have long focused on eradicating asymptomatic carriage as well as disease, resulting in changes in the colonizing microflora with unknown future consequences. Additionally, current vaccines are not easily adaptable to sequence diversity and immune evasion. Here, we present a "smart" vaccine that leverages our current understanding of disease transition from bacterial carriage to infection with the pneumococcus serving as a model organism. Using conserved surface proteins highly expressed during virulent transition, the vaccine mounts an immune response specifically against disease-causing bacterial populations without affecting carriage. Aided by a delivery technology capable of multivalent surface display, which can be adapted easily to a changing clinical picture, results include complete protection against the development of pneumonia and sepsis during animal challenge experiments with multiple, highly variable, and clinically relevant pneumococcal isolates. The approach thus offers a unique and dynamic treatment option readily adaptable to other commensal pathogens.