Cutaneous Delivery of a Live, Attenuated Chimeric Flavivirus Vaccine Against Japanese Encephalitis (ChimeriVax™-JE) in Non-Human Primates

被引:76
作者
Dean, Cheryl H. [1 ]
Alarcon, Jason B. [1 ]
Waterston, Andrea M. [1 ]
Draper, Ken [2 ]
Early, Richard [2 ]
Guirakhoo, Farshad [3 ]
Monath, Thomas P. [3 ]
Mikszta, John A. [1 ]
机构
[1] BD Technol, Res Triangle Pk, NC USA
[2] Charles River Labs, Sierra Div, Sparks, NV USA
[3] Acambis, Cambridge, MA USA
来源
HUMAN VACCINES | 2005年 / 1卷 / 03期
关键词
microneedles; Japanese encephalitis; vaccine; flavivirus; intradermal; epidermal; cutaneous;
D O I
10.4161/hv.1.3.1797
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Flaviviral diseases such as yellow fever, Japanese encephalitis (JE) and dengue hemorrhagic fever cause enormous morbidity and mortality worldwide. There is an urgent need for alternative technologies for mass vaccination against these and other diseases, particularly in the developing world. Here, we administered a live attenuated, chimeric JE vaccine (ChimeriVax (TM)-JE) to nonhuman primates by skin microabrasion and intradermal delivery using microneedles. Both cutaneous delivery methods induced mild viremia similar in magnitude to that observed following subcutaneous (SC) injection. The duration of viremia induced by cutaneous delivery (5-7 days), however, was substantially longer than via SC (0-3 days). In addition, mean neutralizing antibody titers in cutaneous delivery groups were up to 7-fold greater than via SC injection. There were no safety issues identified and both cutaneous delivery methods appeared to be well tolerated. Thus, cutaneous delivery may represent a minimally-invasive alternative approach for flavivirus vaccines that more closely resembles the natural route of viral infection.
引用
收藏
页码:106 / 111
页数:6
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