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Sonden, K.

Publications and source records attributed to Sonden, K..

2 recordsLinked to original sources

Uncovering the genetic diversity of the malaria parasite antigen MSP2 across Sub-Saharan Africa

Genetic diversity in Plasmodium falciparum poses a significant challenge to malaria control and elimination. This is particularly important for developing fully efficacious vaccines, which should include valuable blood stage antigens. Several antigen candidates are highly diverse and require further understanding. We surveyed the genetic diversity of the highly polymorphic merozoite surface protein 2 (MSP2) in 2761 P. falciparum isolates collected across Sub-Saharan Africa. Using PCR-based genotyping and long-read sequencing, we identified extensive diversity among msp2 size variants and sequences. Some size variants were more prevalent than others across different geographical regions, transmission intensities, and time points. These variants comprised multiple unique sequences, of which several were geographically and temporally widespread. Our study reveals greater msp2 sequence diversity than previously known, while also identifying interesting similarities in sequence and gene length across Sub-Saharan Africa. These findings support the further exploration of common msp2 variants in relation to parasite virulence and vaccine development.

microbiology↗

Systems-level analysis of patients treated for acute P. falciparum malaria reveals a role for the humoral response and cytokine milieu in limiting γδ T cell expansion

The mechanism of acquisition and maintenance of natural immunity against Plasmodium falciparum malaria remains unclear. Although, clinical immunity develops over time with repeated malaria episodes, disease tolerance is more rapidly acquired compared to protective immunity. It remains unclear, how pre-existing immune responses impacts the mechanism responsible for disease tolerance. Here, we investigated a cohort of returning travelers treated for acute symptomatic P. falciparum malaria, either infected for the first time, or with a previous history of malaria. Through repeated sampling over one year in a malaria free setting, we were able to study the acute and longitudinal effects of the infection. We combined comprehensive immune cell and plasma protein profiling with integrated and data driven analysis, describing the immune landscape from acute disease to one year after infection. We identified a strong association between pro-inflammatory signatures and {gamma}{delta} T cell expansion. The association was significantly impacted by previous exposure to malaria, resulting in a dampened pro-inflammatory response, which translated to reduced V{delta}2+ {gamma}{delta} T cell expansion compared to primary infected individuals. The dampened inflammatory signal was associated with early expansion of Fc{gamma}RIII+ monocytes and parasite-specific antibodies of IgG1 and IgG3 isotypes. Our data suggest that the interplay of Fc{gamma}RIII+ monocytes and a cytophilic parasite-specific IgG during the early blood stage infection lead to lower parasitemia and a dampened pro-inflammatory response with reduced {gamma}{delta} T cell expansion. This enhanced control and reduced inflammation points to a potential mechanism on how tolerance is established following repeated malaria exposure. One Sentence SummaryA systems immunology analysis on natural malaria sheds light on disease tolerance mechanism associated with gamma delta T cell expansion

immunology↗