Mucosal or systemic administration of rE2 glycoprotein antigen loaded PLGA microspheres.
We have evaluated the ability of recombinant E2 antigen, as a surfactant free formulation of poly (D,L-lactide-co-glycolide) (PLGA) microspheres, to elicit a systemic immune response after administration by mucosal routes (oral and nasal) in comparison to intramuscular route. The sequence encoding a truncated E2 glycoprotein of the classical swine fever virus (CSFV) was expressed in insect cells following infection with recombinant baculovirus, as a His-tagged recombinant antigen. The recombinant E2 glycoprotein (rE2) antigen was co-encapsulated with rabbit serum albumin (RSA) as a protein stabilizer. rE2/RSA loaded PLGA microspheres, with a mean diameter of 4 microm were obtained by a water in oil in water solvent extraction method (w/o/w). Rabbits were immunized with 10 microg of rE2 formulated in PLGA microspheres administrated by three different routes (oral, nasal and intramuscular). After 60 days, each rabbit in all three groups was challenge with 5 microg of rE2 glycoprotein solution by intradermal administration. Blood samples were collected weekly for 90 days and specific rE2 antigen antibodies measured. This work showed that rE2 antigen loaded microspheres was able to initiate an immune response. The intradermal challenge after nasal and oral administration had a clear boost effect on the systemic immune response. Moreover, the response after nasal administration was more intense and less variable than oral route. In conclusion, these data demonstrate a high potential of rE2 loaded PLGA microspheres for their use as a mucosal subunit vaccine.
Laboratoire de Pharmacie Galénique, Biopharmacie et Pharmacie Clinique, UPRES EA 3892, 2 avenue du professeur Léon Bernard 35043 Rennes Cedex, France.
N
N
Brandhonneur
C
C
Loizel
F
F
Chevanne
P
P
Wakeley
A
A
Jestin
M F
MF
Le Potier
P
P
Le Corre
D000281:Administration, Intranasal; D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D000956:Antigens, Viral / Q000008:administration & dosage* / Q000276:immunology; D001682:Biological Availability; D006692:Classical Swine Fever Virus / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology; D007117:Immunization, Secondary; D007136:Immunoglobulins / Q000097:blood / Q000276:immunology; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D019344:Lactic Acid / Q000737:chemistry*; D008863:Microspheres; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics; D012709:Serum Albumin / Q000737:chemistry / Q000493:pharmacokinetics; D014611:Vaccination; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology; D014759:Viral Envelope Proteins / Q000008:administration & dosage* / Q000276:immunology / Q000493:pharmacokinetics; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000276:immunology
D000956:Antigens, Viral; D007136:Immunoglobulins; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C087086:glycoprotein E2, classical swine fever virus; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid