Autologous dendritic cell vaccination against HIV-1 induces changes in natural killer cell phenotype and functionality

Abstract

Although natural killer (NK) cells have been studied in connection with dendritic cell (DC)-based vaccination in the field of cancer immunology, their role has barely been addressed in the context of therapeutic vaccination against HIV-1. In this study, we evaluated whether a therapeutic DC-based vaccine consisting of monocyte-derived DCs electroporated with Tat, Rev and Nef encoding mRNA affects NK cell frequency, phenotype and functionality in HIV-1-infected individuals. Although the frequency of total NK cells did not change, we observed a significant increase in cytotoxic NK cells following immunisation. In addition, significant changes in the NK cell phenotype associated with migration and exhaustion were observed together with increased NK cell-mediated killing and (poly)functionality. Our results show that DC-based vaccination has profound effects on NK cells, which highlights the importance of evaluating NK cells in future clinical trials looking at DC-based immunotherapy in the context of HIV-1 infection.

Unlocking Dendritic Cell-Based Vaccine Efficacy through Genetic Modulation—How Soon Is Now?

“…A concept that seems closer with the development of CRISPR-Cas9-Ribonucleoprotein and macrophage-targeted nano-assembly delivery systems to genetically edit our gene candidates in tumour-associated macrophages in vivo [102]. Such breakthroughs could rapidly expand the application of DC-based therapies beyond cancer to clinical initiatives to fight infectious diseases like HIV [103] or modulate DCs to promote the healing of chronic diabetes ulcers [104]. So, in a bid to answer our original question-How soon is now?-regarding the next generation of DC vaccines capable of generating robust anti-tumour responses: it is close, but important steps remain.…”