IFN-gamma and IL-12 plasmid DNAs as vaccine adjuvant in a murine model of grass allergy.
BACKGROUND
Plasmids encoding cytokines such as IFN-gamma and IL-12 are potential genetic adjuvants that might increase the effectiveness of allergen vaccines.


OBJECTIVE
The role of plasmids expressing the cytokines IFN-gamma (pIFN-gamma) and/or IL-12 (pIL-12) as adjuvants in modulating allergic immune responses, inflammation, and asthma was investigated in a murine model of Kentucky blue grass (KBG) allergy.


METHODS
Groups of naive B6D2F1 mice were vaccinated subcutaneously with KBG allergens and administered intramuscularly with pIFN-gamma, pIL-12, pIFN-gamma plus pIL-12, or a vector control. Mice were then sensitized with KBG allergens in alum (intraperitoneally) and later challenged intranasally. Mice were examined for modulation of specific immunity, prevention of the development of airway hyperresponsiveness, and inflammation.


RESULTS
Mice vaccinated with cytokine plasmid adjuvants had relatively lower levels of total serum IgE and higher levels of grass allergen-specific IgG2a in comparison with control mice. The lowest IgE and highest IgG2a levels were found in mice vaccinated with the combination of pIFN-gamma and pIL-12 as an adjuvant. The vaccination of mice with both pIFN-gamma and pIL-12 as an adjuvant induced the highest level of T(H)1 cytokines, IFN-gamma, and IL-2 in comparison with mice given either of the plasmids alone. The most profound decrease in airway hyperresponsiveness and pulmonary inflammation was observed in mice receiving both pIFN-gamma and pIL-12 as an adjuvant.


CONCLUSIONS
These results demonstrate that pIFN-gamma and pIL-12 together provide an effective adjuvant to parenteral grass allergen vaccines and show that this adjuvant can significantly enhance the effectiveness of allergen immunotherapy in human beings.
Kumar
M
M
Division of Allergy and Immunology-Joy McCann Culverhouse Airway Disease Center, Department of Internal Medicine, University of South Florida College of Medicine, Tampa, FL 33612, USA.
Behera
A K
AK
Hu
J
J
Lockey
R F
RF
Mohapatra
S S
SS
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000818:Animals; D005260:Female; D006967:Hypersensitivity / Q000188:drug therapy*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000235:genetics / Q000627:therapeutic use*; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D010957:Plasmids / Q000627:therapeutic use*; D006109:Poaceae / Q000009:adverse effects*; D012130:Respiratory Hypersensitivity / Q000188:drug therapy; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000276:Adjuvants, Immunologic; D007074:Immunoglobulin G; D018664:Interleukin-12; D007073:Immunoglobulin E; D007371:Interferon-gamma