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首页> 外文期刊>PLoS Pathogens >Trivalent Adenovirus Type 5 HIV Recombinant Vaccine Primes for Modest Cytotoxic Capacity That Is Greatest in Humans with Protective HLA Class I Alleles
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Trivalent Adenovirus Type 5 HIV Recombinant Vaccine Primes for Modest Cytotoxic Capacity That Is Greatest in Humans with Protective HLA Class I Alleles

机译：三价腺病毒5型HIV重组疫苗可引发适度的细胞毒性，这在具有保护性HLA I类等位基因的人类中最大

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If future HIV vaccine design strategies are to succeed, improved understanding of the mechanisms underlying protection from infection or immune control over HIV replication remains essential. Increased cytotoxic capacity of HIV-specific CD8+ T-cells associated with efficient elimination of HIV-infected CD4+ T-cell targets has been shown to distinguish long-term nonprogressors (LTNP), patients with durable control over HIV replication, from those experiencing progressive disease. Here, measurements of granzyme B target cell activity and HIV-1-infected CD4+ T-cell elimination were applied for the first time to identify antiviral activities in recipients of a replication incompetent adenovirus serotype 5 (Ad5) HIV-1 recombinant vaccine and were compared with HIV-negative individuals and chronically infected patients, including a group of LTNP. We observed readily detectable HIV-specific CD8+ T-cell recall cytotoxic responses in vaccinees at a median of 331 days following the last immunization. The magnitude of these responses was not related to the number of vaccinations, nor did it correlate with the percentages of cytokine-secreting T-cells determined by ICS assays. Although the recall cytotoxic capacity of the CD8+ T-cells of the vaccinee group was significantly less than that of LTNP and overlapped with that of progressors, we observed significantly higher cytotoxic responses in vaccine recipients carrying the HLA class I alleles B*27, B*57 or B*58, which have been associated with immune control over HIV replication in chronic infection. These findings suggest protective HLA class I alleles might lead to better outcomes in both chronic infection and following immunization due to more efficient priming of HIV-specific CD8+ T-cell cytotoxic responses.
机译：如果未来的HIV疫苗设计策略能够成功，那么对保护免受感染或对HIV复制的免疫控制的潜在机制的更好理解仍然至关重要。已显示，与有效消除HIV感染的CD4 + T细胞靶标相关的HIV特异性CD8 + T细胞的细胞毒性增加，可将长期非进展者（LTNP），对HIV复制具有持久控制力的患者与经历疾病的患者区分开。在这里，首次应用了颗粒酶B靶细胞活性和HIV-1感染的CD4 + T细胞消除的测定，以鉴定无复制能力的腺病毒血清型5（Ad5）HIV-1重组疫苗接受者的抗病毒活性，并进行了比较。 HIV阴性个体和慢性感染患者，包括一组LTNP。我们在上次免疫后的331天中值观察到了疫苗中容易检测到的HIV特异性CD8 + T细胞召回的细胞毒性反应。这些反应的强度与疫苗接种的数量无关，也与由ICS分析确定的分泌细胞因子的T细胞的百分比无关。尽管被疫苗接种者组的CD8 + T细胞的召回细胞毒能力明显低于LTNP，并与进展者重叠，但我们观察到携带HLA I类等位基因B * 27，B *的疫苗接受者的细胞毒应答明显更高。 57或B * 58，与慢性感染中HIV复制的免疫控制有关。这些发现表明，保护性HLA I类等位基因可能会更有效地引发HIV特异性CD8 + T细胞细胞毒性反应，因此在慢性感染和免疫接种后均可能导致更好的预后。

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