Airway CD8(+) T cells induced by pulmonary DNA immunization mediate protective anti-viral immunity.
Vaccination strategies for protection against a number of respiratory pathogens must induce T-cell populations in both the pulmonary airways and peripheral lymphoid organs. In this study, we show that pulmonary immunization using plasmid DNA formulated with the polymer polyethyleneimine (PEI-DNA) induced antigen-specific CD8(+) T cells in the airways that persisted long after antigen local clearance. The persistence of the cells was not mediated by local lymphocyte proliferation or persistent antigen presentation within the lung or airways. These vaccine-induced CD8(+) T cells effectively mediated protective immunity against respiratory challenges with vaccinia virus and influenza virus. Moreover, this protection was not dependent upon the recruitment of T cells from peripheral sites. These findings demonstrate that pulmonary immunization with PEI-DNA is an efficient approach for inducing robust pulmonary CD8(+) T-cell populations that are effective at protecting against respiratory pathogens.
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA. mbivas@bidmc.harvard.edu
M
M
Bivas-Benita
G O
GO
Gillard
L
L
Bar
K A
KA
White
R J
RJ
Webby
A-H
AH
Hovav
N L
NL
Letvin
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D000941:Antigens / Q000235:genetics / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006801:Humans; D007114:Immunization; D008168:Lung / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009975:Orthomyxoviridae / Q000276:immunology; D010957:Plasmids / Q000235:genetics / Q000276:immunology; D020545:Respiratory Mucosa / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology*; D014780:Viruses / Q000276:immunology*
D000941:Antigens; D018984:Epitopes, T-Lymphocyte; D019444:Vaccines, DNA