Immunization of guinea pigs with novel hepatitis B antigen as nanoparticle aggregate powders administered by the pulmonary route.
Novel nanoparticle-aggregate formulations containing recombinant hepatitis B surface antigen (rHBsAg) were administered to the lungs of guinea pigs and antibodies generated to this antigen evaluated. Preparations of dry powders of: (a) rHBsAg encapsulated within poly(lactic-co-glycolic acid) (PLGA)/polyethylene glycol (PEG) nanoparticles (antigen nanoparticles, AgN(SD)), (b) rHBsAg in a physical mixture with blank PLGA/PEG nanoparticles (antigen nanoparticle admixture (AgNA(SD)), and (c) rHBsAg encapsulated in PLGA/PEG nanoparticles plus free rHBsAg (antigen nanoparticles and free antigen), were generated by spray drying with leucine. Control groups consisted of alum with adsorbed rHBsAg (AlumAg); reconstituted suspensions of spray-dried rHBsAg-loaded PLGA/PEG nanoparticles with leucine; and rHBsAg-loaded PLGA/PEG nanoparticles (AgN). Control preparations were administered by intramuscular injection; AgN was also spray instilled into the lungs. The IgG titers were measured in the serum for 24 weeks after the initial immunization; IgA titers were measured in the bronchio-alveolar lavage fluid. While the highest titer of serum IgG antibody was observed in guinea pigs immunized with AlumAg administered by the IM route, animals immunized with powder formulations via the pulmonary route exhibited high IgA titers. In addition, guinea pigs immunized with AgNA(SD) via the pulmonary route exhibited IgG titers above 1,000 mIU/ml in the serum (IgG titers above 10 mIU/ml is considered protective). Thus, the disadvantages observed with the existing hepatitis B vaccine administered by the parenteral route may be overcome by administering them as novel dry powders to the lungs. In addition, these powders have the advantage of eliciting a high mucosal immune response in the lungs without traditional adjuvants.
Muttil
Pavan
P
Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, North Carolina 27599-7571, USA.
Prego
Cecilia
C
Garcia-Contreras
Lucila
L
Pulliam
Brian
B
Fallon
John Kevin
JK
Wang
Chenchen
C
Hickey
Anthony James
AJ
Edwards
David
D
D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D004797:Enzyme-Linked Immunosorbent Assay; D006168:Guinea Pigs; D006510:Hepatitis B Antibodies / Q000096:biosynthesis; D006511:Hepatitis B Antigens / Q000008:administration & dosage*; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles
D006510:Hepatitis B Antibodies; D006511:Hepatitis B Antigens