Local and systemic immune responses to intratracheal instillation of antigen and DNA vaccines in mice.
OBJECTIVE
The purpose of this study was to determine the immunization efficacy of antigen and DNA vaccines after delivery to the lung, to assess the integrity of the pulmonary tissue after vaccination, and to elucidate mechanisms involved in the induction of immunity.


METHODS
Ovalbumin, the plasmid encoding ovalbumin, the hepatitis B surface antigen (HBsAg), or plasmid encoding HBsAg were intratracheally instilled or injected in quadriceps in mice. The immune response and its Th polarization were analyzed over time. Markers of inflammation were measured in bronchoalveolar lavage, and lung histology was performed. The fate of ovalbumin following intratracheal instillation was studied.


RESULTS
According to the vaccine, the pulmonary route produced stronger or equivalent humoral and cellular responses systemically and locally in the lung as compared to injection. The IgG subclasses and cytokine pattern indicate that the immunity was preferentially polarized toward the Th2 and Th1 type for antigen and DNA immunization, respectively. Ovalbumin penetrated the respiratory tissue and blood poorly after intratracheal instillation, suggesting that the immune response was triggered at airway surfaces. Overall, vaccines delivered to the lung did not induce any local sign of inflammation.


CONCLUSIONS
Pulmonary administration of vaccines might be a promising alternative to conventional vaccination by injection.
Department of Pharmaceutical Technology, School of Pharmacy, Université catholique de Louvain, Brussels, Belgium.
Catherine
C
Lombry
Aline
A
Marteleur
Mohammed
M
Arras
Dominique
D
Lison
Jamila
J
Louahed
Jean-Christophe
JC
Renauld
Véronique
V
Préat
Rita
R
Vanbever
D000818:Animals; D000941:Antigens / Q000008:administration & dosage* / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005260:Female; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000008:administration & dosage / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000145:classification; D007442:Intubation, Intratracheal; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology
D000941:Antigens; D016207:Cytokines; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D010047:Ovalbumin