Plasmids encoding the mucosal chemokines CCL27 and CCL28 are effective adjuvants in eliciting antigen-specific immunity in vivo.
A hurdle facing DNA vaccine development is the ability to generate strong immune responses systemically and at local immune sites. We report a novel systemically administered DNA vaccination strategy using intramuscular codelivery of CCL27 or CCL28, which elicited elevated peripheral IFN-gamma and antigen-specific IgG while driving antigen-specific T-cell secretion of cytokine and antibody production in the gut-associated lymphoid tissue and lung. This strategy resulted in induction of long-lived antibody responses that neutralized influenza A/PR8/34 and protected mice from morbidity and mortality associated with a lethal intranasal viral challenge. This is the first example of the use of CCL27 and CCL28 chemokines as adjuvants to influence a DNA vaccine strategy, suggesting further examination of this approach for manipulation of vaccine-induced immunity impacting both quality and phenotype of responses.
Kutzler
M A
MA
Division of Infectious Diseases and HIV Medicine, The Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USA.
Kraynyak
K A
KA
Nagle
S J
SJ
Parkinson
R M
RM
Zharikova
D
D
Chattergoon
M
M
Maguire
H
H
Muthumani
K
K
Ugen
K
K
Weiner
D B
DB
D000276:Adjuvants, Immunologic; D000818:Animals; D054425:Chemokine CCL27 / Q000276:immunology*; D019742:Chemokines, CC / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D007074:Immunoglobulin G / Q000096:biosynthesis*; D009980:Influenza A virus / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D051379:Mice; D010957:Plasmids; D019444:Vaccines, DNA / Q000276:immunology*
D000276:Adjuvants, Immunologic; C492276:CCL27 protein, human; C414047:CCL28 protein, human; D054425:Chemokine CCL27; D019742:Chemokines, CC; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D007371:Interferon-gamma