Poly[di(carboxylatophenoxy)phosphazene] is a potent adjuvant for intradermal immunization

被引:113
作者
Andrianov, Alexander K. [1 ]
DeCollibus, Daniel P. [1 ]
Gillis, Helice A. [1 ]
Kha, Henry H. [1 ]
Marin, Alexander [1 ]
Prausnitz, Mark R. [2 ]
Babiuk, Lorne A. [3 ,4 ]
Townsend, Hugh [4 ]
Mutwiri, George [4 ]
机构
[1] Apogee Technol Inc, Norwood, MA 02062 USA
[2] Georgia Inst Technol, Sch Chem & Biomol Engn, Atlanta, GA 30332 USA
[3] Univ Alberta, Edmonton, AB T6G 2J9, Canada
[4] Vaccine & Infect Dis Org, Int Vaccine Ctr, Saskatoon, SK S7N 5E3, Canada
关键词
polyphosphazenes; vaccine adjuvants; HEPATITIS-B; INFLUENZA VACCINATION; IMMUNE-RESPONSES; DELIVERY; IMMUNOGENICITY; MICROSPHERES; MICRONEEDLES; PERFORMANCE; TECHNOLOGY; DISRUPTION;
D O I
10.1073/pnas.0908842106
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Intradermal immunization using microfabricated needles represents a potentially powerful technology, which can enhance immune responses and provide antigen sparing. Solid vaccine formulations, which can be coated onto microneedle patches suitable for simple administration, can also potentially offer improved shelf-life. However the approach is not fully compatible with many vaccine adjuvants including alum, the most common adjuvant used in the vaccine market globally. Here, we introduce a polyphosphazene immunoadjuvant as a biologically potent and synergistic constituent of microneedle-based intradermal immunization technology. Poly[di(carboxylatophenoxy)phosphazene], PCPP, functions both as a vaccine adjuvant and as a key microfabrication material. When used as part of an intradermal delivery system for hepatitis B surface antigen, PCPP demonstrates superior activity in pigs compared to intramascular administration and significant antigen sparing potential. It also accelerates the microneedle fabrication process and reduces its dependence on the use of surfactants. In this way, PCPP-coated microneedles may enable effective intradermal vaccination from an adjuvanted patch delivery system.
引用
收藏
页码:18936 / 18941
页数:6
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