Alles Mario, Gunasena Manuja, Isckarus Christina, De Silva Ilmini, Board Sarah, Mulhern Will, Collins Patrick L, Demberg Thorsten, Liyanage Namal P M
bioRxiv. 2024 May 14:2024.05.11.593683. doi: 10.1101/2024.05.11.593683.
Antibody-dependent cell-mediated cytotoxicity, mediated by natural killer (NK) cells and antibodies, emerged as a secondary correlate of protection in the RV144 HIV vaccine clinical trial, the only vaccine thus far demonstrating some efficacy in human. Therefore, leveraging NK cells with enhanced cytotoxic effector responses may bolster vaccine induced protection against HIV. Here, we investigated the effect of orally administering indole-3-carbinol (I3C), an aryl hydrocarbon receptor (AHR) agonist, as an adjuvant to an RV144-like vaccine platform in a mouse model. We demonstrate the expansion of KLRG1-expressing NK cells induced by the vaccine together with I3C. This NK cell subset exhibited enhanced vaccine antigen-specific cytotoxic memory-like features. Our study underscores the potential of incorporating I3C as an oral adjuvant to HIV vaccine platforms to enhance antigen-specific (memory-like) cytotoxicity of NK cells against HIV-infected cells. This approach may contribute to enhancing the protective efficacy of HIV preventive vaccines against HIV acquisition.
由自然杀伤（NK）细胞和抗体介导的抗体依赖性细胞介导的细胞毒性，在RV144 HIV疫苗临床试验中作为保护的次要相关因素出现，这是迄今为止唯一一种在人体中显示出一定疗效的疫苗。因此，利用具有增强细胞毒性效应反应的NK细胞可能会增强疫苗诱导的针对HIV的保护作用。在此，我们在小鼠模型中研究了口服吲哚 - 3 - 甲醇（I3C）（一种芳烃受体（AHR）激动剂）作为RV144样疫苗平台佐剂的效果。我们证明了疫苗与I3C共同诱导表达KLRG1的NK细胞扩增。该NK细胞亚群表现出增强的疫苗抗原特异性细胞毒性记忆样特征。我们的研究强调了将I3C作为HIV疫苗平台口服佐剂以增强NK细胞对HIV感染细胞的抗原特异性（记忆样）细胞毒性的潜力。这种方法可能有助于提高HIV预防性疫苗预防HIV感染的保护效力。
