Pre-Existing Adenovirus Immunity Modifies a Complex Mixed Th1 and Th2 Cytokine Response to an Ad5/HIV-1 Vaccine Candidate in Humans
Pre-Existing Adenovirus Immunity Modifies a Complex Mixed Th1 and Th2 Cytokine Response to an Ad5/HIV-1 Vaccine Candidate in Humans
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DOI：
10.1371/journal.pone.0018526
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发表时间：
2011-04-13
期刊：
影响因子：
3.7
通讯作者：
McElrath, M. Juliana
中科院分区：
文献类型：
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作者：
Pine, Samuel O.;Kublin, James G.;McElrath, M. Juliana
最近的步骤研究的结果强调了需要澄清预先存在的天然免疫对疫苗载体对疫苗诱导的T细胞应答的影响。为了研究这种相互作用，我们在健康的、未感染HIV的MRKAd 5 HIV-1 gag疫苗（HVTN 050，ClinicalTrials.gov）接受者中检查了预先存在的Ad 5免疫和T细胞细胞因子应答谱之间的关系。根据基线Ad 5中和抗体滴度将参与者分组为Ad 5血清阴性（滴度200; n = 34）。使用在不存在长期培养物的情况下测量三十种细胞因子的离体测定，分析来自疫苗接受者的样品对HIV-1 Gag肽库或Ad 5空载体的免疫应答。对Gag和Ad 5的细胞因子应答的总体概况具有诱导的Th 1和Th 2型细胞因子的相似组合，包括IFN-γ、IL-2、TNF-α、IP-10、IL-13和IL-10，尽管Ad 5特异性应答一致地高于Gag特异性应答（p
The results of the recent Step Study highlight a need to clarify the effects of pre-existing natural immunity to a vaccine vector on vaccine-induced T-cell responses. To investigate this interaction, we examined the relationship between preexisting Ad5 immunity and T-cell cytokine response profiles in healthy, HIV-uninfected recipients of MRKAd5 HIV-1 gag vaccine (HVTN 050, ClinicalTrials.gov #NCT00849732). Participants were grouped by baseline Ad5 neutralizing antibody titer as either Ad5-seronegative (titer 200; n = 34). Samples from vaccine recipients were analyzed for immune responses to either HIV-1 Gag peptide pools or Ad5 empty vector using an ex vivo assay that measures thirty cytokines in the absence of long-term culture. The overall profiles of cytokine responses to Gag and Ad5 had similar combinations of induced Th1- and Th2-type cytokines, including IFN-gamma, IL-2, TNF-alpha, IP-10, IL-13, and IL-10, although the Ad5-specific responses were uniformly higher than the Gag-specific responses (p