Downregulation of IgE antibody and allergic responses in the lung by epidermal biolistic microparticle delivery.
BACKGROUND
Biolistic injections provide a needle-free delivery of antigen-laden microparticles to the epithelium. The precision of the injection preferentially targets the Langerhans cell network, which, although ideal for vaccination, might not be suitable for the downregulation of immune responses in immunotherapy.


OBJECTIVE
We sought to determine the ability of biolistic injection of antigen into the epithelium of sensitized mice to inhibit IgE antibody and lung inflammatory responses produced by further exposure to antigen.


METHODS
Mice were sensitized by means of a needle injection of ovalbumin (OVA) in alum and given a series of biolistic injections of OVA or vehicle control, followed by a boost of OVA in alum. Serum IgE and IgG antibodies were measured before and after the boost. The mice were then challenged intranasally, and the infiltration of inflammatory cells was measured by means of bronchoalveolar lavage. Airway reactivity of the challenged mice was measured by examining responses to methacholine with forced oscillatory techniques.


RESULTS
Biolistic injection of OVA into the dorsal skin of sensitized mice markedly inhibited IgE and IgG1 antibody responses induced by boosting. IgG2a antibody responses were reduced rather than stimulated. The eosinophilic inflammation in the bronchoalveolar lavage fluid induced by intranasal challenge was also markedly inhibited. Lung hyperreactivity showed an initial increase and then a decrease of responsiveness to methacholine, with elastance returning to the level of unsensitized mice. Biolistic injection into the buccal epithelium was also inhibitory.


CONCLUSIONS
Biolistic injection of allergen inhibited the boosting of IgE antibody and eosinophilic lung inflammatory responses without inducing T(H)1 immunity.
Kendall
Mark
M
The PowderJect Centre for Gene and Drug Delivery Research, University of Oxford, UK.
Mitchell
Thomas J
TJ
Costigan
George
G
Armitage
Mark
M
Lenzo
Jason C
JC
Thomas
Jennifer A
JA
von Garnier
Christophe
C
Zosky
Graeme R
GR
Turner
Debra J
DJ
Stumbles
Phil A
PA
Sly
Peter D
PD
Holt
Patrick G
PG
Thomas
Wayne R
WR
D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology; D019470:Biolistics / Q000379:methods*; D003888:Desensitization, Immunologic / Q000379:methods*; D015536:Down-Regulation; D004802:Eosinophilia; D004817:Epidermis; D005260:Female; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000096:biosynthesis*; D007074:Immunoglobulin G / Q000096:biosynthesis; D008168:Lung / Q000276:immunology* / Q000502:physiology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009061:Mouth Mucosa; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D013047:Specific Pathogen-Free Organisms
D000941:Antigens; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin