Relevance of a pre-existing measles immunity prior immunization with a recombinant measles virus vector
Relevance of a pre-existing measles immunity prior immunization with a recombinant measles virus vector
复制标题
DOI：
10.4161/hv.23241
复制
发表时间：
2013-03-01
影响因子：
4.8
通讯作者：
Naim, Hussein Y.
中科院分区：
文献类型：
--
作者：
Knuchel, Marlyse C.;Marty, Rene R.;Naim, Hussein Y.
麻疹病毒（MV）载体是设计新型重组疫苗的有希望的候选者，因为亲本活疫苗具有众所周知的安全性和有效性记录。与所有病毒载体一样，MV 载体诱导保护性免疫反应的功效可能会受到人群中预先存在的免疫力的影响。为了确定最佳免疫途径和方案，我们通过在用表达 SIV-gag 抗原 (rMV-SIVgag) 的重组 MV 进行肌内 (i.m.) 和/或鼻内 (i.n.) 免疫之前被动施用 MV 中和抗体 (MV-nAb) 来模拟 MV 预免疫。我们的结果显示，500 mIU 的 MV-nAb 可以诱导针对载体和转基因的体液和细胞免疫应答，而更高滴度的 MV-nAb 具有显着的抑制作用。在初免-加强方案中，在 MV-nAb 存在的情况下，鼻内-肌内 (i.n.-i.m.) 或肌内-肌内 (i.m.-i.m.) 途径诱导针对载体和转基因 (SIV-gag) 的更高体液免疫反应。在幼稚动物中，肌内注射后细胞免疫反应显着升高。免疫接种；然而，MV 免疫前似乎并不影响注射后的细胞免疫反应。总之，我们表明，高达 500 mIU 的抗 MV 中和抗体的预先存在的免疫力对 rMV 的复制几乎没有影响，并且不会抑制免疫活性小鼠中显着体液和细胞免疫反应的诱导。
Measles virus (MV) vectors are promising candidates for designing new recombinant vaccines since the parental live vaccines have a well-known safety and efficacy record. Like all viral vectors, the MV vector efficacy in inducing a protecting immune answer could be affected by the pre-existing immunity among the human population. In order to determine the optimal immunization route and regimen, we mimicked a MV pre-immunity by passively administrating MV neutralizing antibodies (MV-nAb) prior intramuscular (i.m.) and/or intranasal (i.n.) immunization with recombinant MV expressing the SIV-gag antigen (rMV-SIVgag). Our results revealed that 500 mIU of MV-nAb allowed the induction of a humoral and cellular immune response against the vector and the transgene, while higher titers of the MV-nAb were significantly inhibitory. In a prime-boost regimen, in the presence of MV-nAb, the intranasal-intramuscular (i.n.-i.m.) or intramuscular-intramuscular (i.m.-i.m.) routes induced higher humoral immune responses against the vector and the transgene (SIV-gag). In naive animals, cellular immune response was significantly higher by i.m. immunization; however, MV pre-immunity did not seem to affect the cellular immune response after an i.n. immunization.In summary, we show that a pre-existing immunity of up to 500 mIU anti-MV neutralizing antibodies had little effect on the replication of rMV and did not inhibit the induction of significant humoral and cellular immune responses in immune-competent mice.