Malaria is a hazardous disease caused by Plasmodium parasites and often results in lethal complications, including malaria-associated acute respiratory distress syndrome (MA-ARDS). Parasite sequestration in the microvasculature is often observed, but its role in malaria pathogenesis and complications is still incompletely understood. We used skeleton binding protein-1 (SBP-1) KO parasites to study the role of sequestration in experimental MA-ARDS. The sequestration-deficiency of these SBP-1 KO parasites was confirmed with bioluminescence imaging and by measuring parasite accumulation in the lungs with RT-qPCR. The SBP-1 KO parasites induced similar lung pathology in the early stage of experimental MA-ARDS compared to wildtype (WT) parasites. Strikingly, the lung pathology resolved subsequently in more than 60% of the SBP-1 KO infected mice, resulting in prolonged survival despite the continuous presence of the parasite. This spontaneous disease resolution was associated with decreased inflammatory cytokine expression measured by RT-qPCR and lower expression of cytotoxic markers in pathogenic CD8+ T cells in the lungs of SBP-1 KO infected mice. These data suggest that SBP-1-mediated parasite sequestration and subsequent high parasite load are not essential for the development of experimental MA-ARDS but inhibit the resolution of the disease.

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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.

Objective(s):Suppression of viral replication in patients on antiretroviral therapy (ART) is determined by plasma viral load (pVL) measurement. Whenever pVL reaches values below the limit of quantification, the qualitative parameter ’target detected’ or ’target not detected’ is available but often not reported to the clinician. We investigated whether qualitative pVL measurements can be used to estimate the viral reservoir size.Design:The study recruited 114 people with HIV (PWH) who are stable on ART between 2016 and 2018. The percentage of pVL measurements qualitatively reported as ’target detected’ (PTD) within a 2-year period was calculated.Methods:t-DNA and US-RNA were used to estimate viral reservoir size and were quantified on peripheral blood mononuclear cells (PBMCs) using droplet digital PCR.Results:A median of 6.5 pVL measurements over a 2-year period was evaluated for each participant to calculate PTD. A positive correlation was found between t-DNA and PTD (r = 0.24; P = 0.011) but not between US-RNA and PTD (r = 0.1; P = 0.3). A significantly lower PTD was observed in PWH with a small viral reservoir, as estimated by t-DNA less than 66 copies/106 PBMCs and US-RNA less than 10 copies/106 PBMCs, compared with PWH with a larger viral reservoir (P = 0.001). We also show that t-DNA is detectable whenever PTD is higher than 56% and that ART regimen does not affect PTD.Conclusion:Our study shows that PTD provides an efficient parameter to preselect participants with a small viral reservoir based on already available pVL data for future HIV cure trials.