Effect of preexisting immunity to adenovirus human serotype 5 antigens on the immune responses of nonhuman primates to vaccine regimens based on human- or chimpanzee-derived adenovirus vectors
Effect of preexisting immunity to adenovirus human serotype 5 antigens on the immune responses of nonhuman primates to vaccine regimens based on human- or chimpanzee-derived adenovirus vectors
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DOI：
10.1128/jvi.02497-06
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发表时间：
2007-06-01
影响因子：
5.4
通讯作者：
Ertl, Hildegund C. J.
中科院分区：
文献类型：
--
作者：
McCoy, Kimberly;Tatsis, Nia;Ertl, Hildegund C. J.
在这项研究中，我们比较了两个血清学上不同的复制缺陷型腺病毒（Ad）载体来自黑猩猩血清型C68和C1表达Gag，Pol，gp 140和Nef的人类免疫缺陷病毒I型的方案，其中复制缺陷型腺病毒载体的人血清型5（AdHu 5）给予两次的初免-加强方案。在已经或没有预先暴露于AdHu 5抗原的恒河猴中进行实验。从不同组的外周血中检测的T细胞应答没有显著差异，尽管在用黑猩猩Ad载体免疫的未预先暴露的动物中应答总体上最高。预先存在的免疫AdHu 5完全抑制诱导转基因产品特异性抗体的AdHu 5载体，而不影响抗体反应的黑猩猩载体。安乐死后，从许多组织中检测T细胞应答。预先存在的对AdHuS的免疫力，通常在人类中发现，改变了疫苗诱导的T细胞的归巢模式。在AdHu 5预暴露的动物接种黑猩猩Ad载体，转基因特异性T细胞的频率在脾脏比在血液中更高，在大多数预暴露的动物接种AdHu 5载体或黑猩猩腺病毒载体，这样的T细胞的频率是非常高的肝脏。后者的结果表明，仅从疫苗接种者的血液单核细胞的T细胞反应的分析可能不足以比较不同的疫苗方案的效力。
In this study we compared a prime-boost regimen with two serologically distinct replication-defective adenovirus (Ad) vectors derived from chimpanzee serotypes C68 and C1 expressing Gag, Pol, gp140, and Nef of human immunodeficiency virus type I with a regimen in which replication-defective Ad vectors of the human serotype 5 (AdHu5) were given twice. Experiments were conducted in rhesus macaques that had or had not been preexposed to antigens of AdHu5. There was no significant difference in T-cell responses tested from peripheral blood of the different groups, although responses were overall highest in nonpreexposed animals immunized with the chimpanzee Ad vectors. Preexisting immunity to AdHu5 completely inhibited induction of transgene product-specific antibodies by the AdHu5 vectors without affecting antibody responses to the chimpanzee vectors. Upon euthanasia, T-cell responses were tested from a number of tissues. Preexisting immunity to AdHuS, commonly found in humans, changed the homing pattern of vaccine-induced T cells. In AdHu5-preexposed animals vaccinated with the chimpanzee Ad vectors, frequencies of transgene-specific T cells were higher in spleens than in blood, and in most preexposed animals vaccinated either with AdHu5 vectors or chimpanzee adenovirus vectors, frequencies of such T cells were exceptionally high in livers. The latter results indicate that analysis of T-cell responses solely from blood mononuclear cells of vaccine recipients may not suffice to compare the potencies of different vaccine regimens.