Directed vaccination against pneumococcal disease.
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.
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260;
Yi
Y
Li
Abcombi Biosciences Inc., Buffalo, NY 14260;
Andrew
A
Hill
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260;
Marie
M
Beitelshees
Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260;
Shuai
S
Shao
Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260;
Jonathan F
0000-0002-9052-884X
JF
Lovell
Department of Anesthesiology, University at Buffalo, The State University of New York, Buffalo, NY 14260;
Bruce A
0000-0001-8223-1870
BA
Davidson
Department of Anesthesiology, University at Buffalo, The State University of New York, Buffalo, NY 14260; Department of Microbiology and Immunology, University at Buffalo, The State University of New York, Buffalo, NY 14260;
Paul R
PR
Knight
Department of Microbiology and Immunology, University at Buffalo, The State University of New York, Buffalo, NY 14260; Division of Experimental Infection Medicine, Department of Laboratory Medicine, Lund University, SE-221 00 Malmo, Sweden blainepf@buffalo.edu Anders_P.Hakansson@med.lu.se charles.jones@abcombibio.com.
Anders P
AP
Hakansson
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY 14260; Abcombi Biosciences Inc., Buffalo, NY 14260; blainepf@buffalo.edu Anders_P.Hakansson@med.lu.se charles.jones@abcombibio.com.
Blaine A
BA
Pfeifer
Abcombi Biosciences Inc., Buffalo, NY 14260; blainepf@buffalo.edu Anders_P.Hakansson@med.lu.se charles.jones@abcombibio.com.
Charles H
CH
Jones
D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis; D018441:Biofilms; D006801:Humans; D051379:Mice; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000276:immunology
D000907:Antibodies, Bacterial; D022242:Pneumococcal Vaccines
S. pneumoniae; biofilm; pneumococcal; vaccine; virulence