PNAS – Proceedings of the National Academy of Sciences of the United States of America
http://www.pnas.org/content/early/
(Accessed 11 June 2016)

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Biological Sciences – Applied Biological Sciences:
Directed vaccination against pneumococcal disease
Yi Li, Andrew Hill, Marie Beitelshees, Shuai Shao, Jonathan F. Lovell, Bruce A. Davidson, Paul R. Knight III, Anders P. Hakansson, Blaine A. Pfeifer, and Charles H. Jones
PNAS 2016 ; published ahead of print June 6, 2016, doi:10.1073/pnas.1603007113

Significance
Pneumococcal disease represents a global health problem, especially for the young, the elderly, and the resource-limited. Disease progression begins with asymptomatic nasopharyngeal bacterial colonization before subsequent dissemination and disease (pneumonia, sepsis, and middle ear infection). Analysis of this transition from colonization to disease provided antigens that were tested in this study for directed vaccination against only the virulent subset of pneumococci. In so doing, a “smart” vaccine was sought that would address this disease broadly, effectively, and selectively.

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.