Abstract:
PURPOSE:With the aim of developing multivalent vaccines for single-injection, we examined the feasibility of combining antigens in biodegradable microspheres. Such vaccines are expected to improve vaccination coverage by reducing the number of vaccination sessions required to generate immunity. METHODS:Mono- and multivalent vaccines of Haemophilus influenzae type b (Hib) conjugate, diphtheria toxoid (DT), tetanus toxoid (TT), and pertussis toxin (PT) in poly (lactic acid) and poly(lactic-coglycolic acid) microspheres were prepared by spray drying, and the influence of coencapsulated antigens and excipients on antigen loading, release, and stability was examined. Two tetravalent formulations were tested in guinea pigs. RESULTS:Monovalent Hib and PT vaccines showed loading efficiencies of 10% (Hib) and 30% (PT) in both polymers. The loading efficiencies increased upon addition of trehalose and, even more, when the antigens were coencapsulated in di- and trivalent combinations. Highest loading efficiencies (> 80%) were achieved with trivalent formulations (DT + PT + Hib) that also contained coencapsulated albumin. The percentage of antigen released during 24 h of incubation was typically 10-40% and decreased as loading efficiency increased. Enzyme-linked immunosorbent assay (ELISA) data revealed that TT, DT, and PT remained antigenic throughout the encapsulation and subsequent release processes. Finally, all antigens maintained their immunogenicity, since strong and sustained antibody responses were elicited after a single injection of tetravalent microsphere vaccines (DT + TT + PT + Hib) in guinea pigs. CONCLUSIONS:This study reveals technologic benefit as well as an immunological potential of multivalent single-injection microsphere vaccines. The results support our hypothesis that coencapsulation of several antigens may intrinsically improve entrapment of antigenic and immunogenic antigen probably by virtue of increased protein concentration during microencapsulation leading to mutual stabilization of the components.
journal_name
Pharm Resjournal_title
Pharmaceutical researchauthors
Boehm G,Peyre M,Sesardic D,Huskisson RJ,Mawas F,Douglas A,Xing D,Merkle HP,Gander B,Johansen Pdoi
10.1023/a:1020354809581subject
Has Abstractpub_date
2002-09-01 00:00:00pages
1330-6issue
9eissn
0724-8741issn
1573-904Xjournal_volume
19pub_type
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