Mucosal and systemic adjuvant activity of alphavirus replicon particles

被引:73
作者
Thompson, JM
Whitmore, AC
Konopka, JL
Collier, ML
Richmond, EMB
Davis, NL
Staats, HF
Johnston, RE [1 ]
机构
[1] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Carolina Vaccine Inst, Chapel Hill, NC 27599 USA
[3] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA
[4] Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA
[5] Duke Univ, Med Ctr, Human Vaccine Inst, Durham, NC 27710 USA
关键词
vaccine vector; Venezuelan equine encephalitis virus; viral immunology; RNA virus;
D O I
10.1073/pnas.0600287103
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
Vaccination represents the most effective control measure in the fight against infectious diseases. Local mucosal immune responses are critical for protection from, and resolution of, infection by numerous mucosal pathogens. Antigen processing across mucosal surfaces is the natural route by which mucosal immunity is generated, as peripheral antigen delivery typically fails to induce mucosal immune responses. However, we demonstrate in this article that mucosal immune responses are evident at multiple mucosal surfaces after parenteral delivery of Venezuelan equine encephalitis virus replicon particles (VRP). Moreover, coinoculation of null VRP (not expressing any transgene) with inactivated influenza virions, or ovalbumin, resulted in a significant increase in antigen-specific systemic IgG and fecal IgA antibodies, compared with antigen alone. Pretreatment of VRP with UV light largely abrogated this adjuvant effect. These results demonstrate that alphavirus replicon particles possess intrinsic systemic and mucosal adjuvant activity and suggest that VRP RNA replication is the trigger for this activity. We feel that these observations and the continued experimentation they stimulate will ultimately define the specific components of an alternative pathway for the induction of mucosal immunity, and if the activity is evident in humans, will enable new possibilities for safe and inexpensive subunit and inactivated vaccines.
引用
收藏
页码:3722 / 3727
页数:6
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