Comparative immunogenicity in rhesus monkeys of DNA plasmid, recombinant vaccinia virus, and replication-defective adenovirus vectors expressing a human immunodeficiency virus type 1 gag gene
Comparative immunogenicity in rhesus monkeys of DNA plasmid, recombinant vaccinia virus, and replication-defective adenovirus vectors expressing a human immunodeficiency virus type 1 gag gene
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DOI：
10.1128/jvi.77.11.6305-6313.2003
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发表时间：
2003-06-01
影响因子：
5.4
通讯作者：
Shiver, JW
中科院分区：
文献类型：
--
作者：
Casimiro, DR;Chen, L;Shiver, JW
细胞免疫反应，特别是与CD3(+)CD8(+)细胞毒性T淋巴细胞(CTL)相关的免疫反应，在控制病毒感染，包括持续感染人类免疫缺陷病毒1型(HIV-1)方面发挥着主要作用。因此，最近的HIV-1疫苗研究工作集中在建立诱导这种抗病毒CTL免疫反应的最佳方法上。我们评估了几种DNA疫苗配方，改良的痘苗病毒安卡拉载体和复制缺陷型5型腺病毒(Ad5)载体，每种载体都表达相同的密码子优化的HIV-1 Gag基因对恒河猴的免疫原性。DNA疫苗是用和不用两种化学佐剂(磷酸铝和CRL1005)中的一种配制的。Ad5-GAG载体诱导的抗GAG CTL效果最好。该疫苗同时产生了CD4(+)和CD8(+)T细胞反应，后者始终是主要成分。为了确定现有的抗腺病毒免疫对腺病毒5Gag诱导的免疫反应的影响，在用Ad5-Gag免疫猴子之前，将猴子暴露于不编码抗原的5型腺病毒。由此产生的抗Gag T细胞反应减弱了，但并未被消除。还比较了先用不同的DNA疫苗配方启动，然后用腺病毒载体加强免疫的方案。在测试的制剂中，DNA-CRL1005疫苗最有效地激发T细胞反应，并在增强Ad5-GAG后提供最好的整体免疫反应。这些结果提示了一种以使用腺病毒载体为中心的人类免疫策略，在这种策略中，现有的腺病毒免疫可以通过佐剂DNA和腺病毒载体增强的联合免疫来克服。
Cellular immune responses, particularly those associated with CD3(+) CD8(+) cytotoxic T lymphocytes (CTL), play a primary role in controlling viral infection, including persistent infection with human immunodeficiency virus type 1 (HIV-1). Accordingly, recent HIV-1 vaccine research efforts have focused on establishing the optimal means of eliciting such antiviral CTL immune responses. We evaluated several DNA vaccine formulations, a modified vaccinia virus Ankara vector, and a replication-defective adenovirus serotype 5 (Ad5) vector, each expressing the same codon-optimized HIV-1 gag gene for immunogenicity in rhesus monkeys. The DNA vaccines were formulated with and without one of two chemical adjuvants (aluminum phosphate and CRL1005). The Ad5-gag vector was the most effective in eliciting anti-Gag CTL. The vaccine produced both CD4(+) and CD8(+) T-cell responses, with the latter consistently being the dominant component. To determine the effect of existing antiadenovirus immunity on Ad5-gag-induced immune responses, monkeys were exposed to adenovirus subtype 5 that did not encode antigen prior to immunization with Ad5-gag. The resulting anti-Gag T-cell responses were attenuated but not abolished. Regimens that involved priming with different DNA vaccine formulations followed by boosting with the adenovirus vector were also compared. Of the formulations tested, the DNA-CRL1005 vaccine primed T-cell responses most effectively and provided the best overall immune responses after boosting with Ad5-gag. These results are suggestive of an immunization strategy for humans that are centered on use of the adenovirus vector and in which existing adenovirus immunity may be overcome by combined immunization with adjuvanted DNA and adenovirus vector boosting.