Th17-stimulating protein vaccines confer protection against Pseudomonas aeruginosa pneumonia.
BACKGROUND
New vaccine approaches are needed for Pseudomonas aeruginosa, which continues to be a major cause of serious pulmonary infections. Although Th17 cells can protect against gram-negative pathogens at mucosal surfaces, including the lung, the bacterial proteins recognized by Th17 cells are largely unknown and could be potential new vaccine candidates.


OBJECTIVE
We describe a strategy to identify Th17-stimulating protein antigens of Pseudomonas aeruginosa to assess their efficacy as vaccines against pneumonia.


METHODS
Using a library of in vitro transcribed and translated P. aeruginosa proteins, we screened for Th17-stimulating antigens by coculturing the library proteins with splenocytes from mice immunized with a live-attenuated P. aeruginosa vaccine that is protective via Th17-based immunity. We measured antibody and Th17 responses after intranasal immunization of mice with the purified proteins mixed with the Th17 adjuvant curdlan, and we tested the protective efficacy of vaccination in a murine model of acute pneumonia.


RESULTS
The proteins PopB, FpvA, FptA, OprL, and PilQ elicited strong IL-17 secretion in the screen, and purified versions of PopB, FpvA, and OprL stimulated high IL-17 production from immune splenocytes. Immunization with PopB, which is a highly conserved component of the type III secretion system and a known virulence factor, elicited Th17 responses and also enhanced clearance of P. aeruginosa from the lung and spleen after challenge. PopB-immunized mice were protected from lethal pneumonia in an antibody-independent, IL-17-dependent manner.


CONCLUSIONS
Screening for Th17-stimulating protein antigens identified PopB as a novel and promising vaccine candidate for P. aeruginosa.
Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA.
Weihui
W
Wu
Jin
J
Huang
Biyan
B
Duan
David C
DC
Traficante
Haeyeon
H
Hong
Martina
M
Risech
Stephen
S
Lory
Gregory P
GP
Priebe
D000818:Animals; D000907:Antibodies, Bacterial / Q000378:metabolism; D000942:Antigens, Bacterial / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D004195:Disease Models, Animal; D051379:Mice; D018410:Pneumonia, Bacterial / Q000276:immunology*; D011552:Pseudomonas Infections / Q000276:immunology*; D054406:Pseudomonas Vaccines; D011550:Pseudomonas aeruginosa / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D058504:Th17 Cells / Q000378:metabolism*; D014613:Vaccines, Attenuated
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C576076:PopB protein, Pseudomonas aeruginosa; D054406:Pseudomonas Vaccines; D014613:Vaccines, Attenuated