Fabrication of cell culture-derived influenza vaccine dissolvable microstructures and evaluation of immunogenicity in guinea pigs.
Microstructure patches provide an opportunity for simple, effective, and safe vaccine administration, while achieving the desired immune response. We have evaluated the MicroCor transdermal system for cell culture-derived trivalent influenza vaccine administration. Influenza monovalent purified bulk vaccines (monobulks) (H1N1, H3N2, B) were concentrated by tangential flow filtration, lyophilized, and formulated with biocompatible excipients to form the microstructure array dissolvable tips. Standard single radial immunodiffusion (SRID) determined that the influenza antigens retained potency through the formulation and microstructure array fabrication processes. Array stability was evaluated for storage in both refrigerated and room temperature conditions. Microstructure mechanical strength was confirmed by application to excised pig skin, resulting in successful skin penetration and tip dissolution within 5 min of microstructure insertion. Guinea pigs immunized with influenza vaccine-loaded microstructures had hemagglutinin inhibition (HI) and IgG titers comparable to those obtained by intramuscular injection. After two immunizations, serum HI titers for all immunized groups were greater than 40 (>4-fold higher than the untreated group). These data demonstrate the feasibility for the development of skin delivery technologies that are compatible with cell culture-derived influenza vaccines.
Vaccines Research, Novartis Vaccines, Cambridge, MA 02139, USA.
Amanda
A
Bonificio
Corium International, Inc., Menlo Park, CA 94025, USA.
Esi
E
Ghartey-Tagoe
Vaccines Research, Novartis Vaccines, Siena 53100, Italy.
Simona
S
Gallorini
Vaccines Research, Novartis Vaccines, Siena 53100, Italy.
Barbara
B
Baudner
Corium International, Inc., Menlo Park, CA 94025, USA.
Guohua
G
Chen
Corium International, Inc., Menlo Park, CA 94025, USA.
Parminder
P
Singh
Vaccines Research, Novartis Vaccines, Cambridge, MA 02139, USA.
Derek T
DT
O'Hagan
Vaccines Research, Novartis Vaccines, Cambridge, MA 02139, USA. Electronic address: sushma.kommareddy@novartis.com.
Sushma
S
Kommareddy
D000279:Administration, Cutaneous; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000097:blood / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D006168:Guinea Pigs; D006385:Hemagglutination Inhibition Tests; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology; D006801:Humans; D005779:Immunodiffusion; D007074:Immunoglobulin G / Q000097:blood; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053122:Influenza A Virus, H3N2 Subtype / Q000276:immunology*; D009981:Influenza B virus / Q000276:immunology*; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000276:immunology*; D007251:Influenza, Human / Q000517:prevention & control; D009976:Orthomyxoviridae Infections / Q000517:prevention & control; D014611:Vaccination
D000914:Antibodies, Viral; D000956:Antigens, Viral; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D007252:Influenza Vaccines
Dissolvable; Influenza vaccine; Microneedles; Microstructures; Skin delivery