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Inklaar, M. R.

Publications and source records attributed to Inklaar, M. R..

3 recordsLinked to original sources

Blood, sweat, and beers: investigating mosquito biting preferences amidst noise and intoxication in a cross-sectional cohort study at a large music festival

IntroductionWe live in a world split between mosquito magnets and those lucky enough to remain (nearly) untouched. The reasons why some people attract more mosquito bites than others remain largely mysterious. In the Mosquito Magnet Trial, we investigated differences in mosquito attraction amongst festivalgoers with varying levels of hygiene and intoxication. MethodsOur study was conducted in a slightly steamy pop-up laboratory inside four connected shipping containers at Lowlands Festival in The Netherlands (August 18-20, 2023). Participants completed an anonymous questionnaire on hygiene, diet, and festival-related behaviour (including alcohol uptake and shared sleeping arrangements). Mosquito attraction was measured using a custom designed setup: a transparent cage with perforations where female Anopheles mosquitoes were offered a choice between a sugar-feeder and the participants arm. Mosquitoes could only smell, not bite, the participants arm. Attraction was quantified through video imaging, measuring arm landings relative to total landings. Mosquito attraction was correlated with questionnaire responses and skin microbiota profiles collected from forearm skin swabs. ResultsAmongst the 465 included participants, mosquitoes showed a clear fondness for those who drank beer over those who abstained from the liquid gold (Fold Change 1.35, 95% CI 1.12-1.63, PFDR<0.001). Attraction was also contagious: participants that successfully lured a fellow human into their tent the previous night also proved more enticing to mosquitoes (FC 1.34, 95% CI 1.14-1.58, PFDR=0.002). Meanwhile, skipping the morning showering routine and using sunscreen reduced mosquito attraction (FC 0.52, 95% 0.38-0.70, PFDR<0.001). Streptococci were more abundant on the skin of highly attractive individuals (Puncorrected=0.017), and the overall abundance of malodour associated bacteria was high - possibly reflecting the containers smell. ConclusionThe Mosquito Magnet Trial, to our knowledge the largest study of its kind, was conducted in a loosely controlled setting with a selection bias towards science loving festivalgoers. That said, using our custom designed experimental set-up, we found that mosquitoes are drawn to those who avoid sunscreen, drink beer, and share their bed. They simply have a taste for the hedonists among us.

animal behavior and cognition↗

Structure of endogenous Pfs230:Pfs48/45 in complex with potent malaria transmission-blocking antibodies

The Pfs230:Pfs48/45 complex forms the basis for leading malaria transmission-blocking vaccine candidates, yet li]le is known about its molecular assembly. Here, we used cryogenic electron microscopy to elucidate the structure of the endogenous Pfs230:Pfs48/45 complex bound to six potent transmission-blocking antibodies. Pfs230 consists of multiple domain clusters rigidified by interactions mediated through insertion domains. Membrane-anchored Pfs48/45 forms a disc-like structure and interacts with a short C-terminal peptide on Pfs230 that is critical for Pfs230 membrane-retention in vivo. Interestingly, membrane retention through this interaction is not essential for transmission to mosquitoes, suggesting that complex disruption is not a mode of action for transmission-blocking antibodies. Analyses of Pfs48/45-and Pfs230-targeted antibodies identify conserved epitopes on the Pfs230:Pfs48/45 complex and provides a structural paradigm for complement-dependent activity of Pfs230-targeting antibodies. Altogether, the antibody-bound Pfs230:Pfs48/45 structure presented improves our molecular understanding of this biological complex, informing the development of next-generation Plasmodium falciparum transmission-blocking interventions.

molecular biology↗

Pfs230 Domain 12 is a potent malaria transmission-blocking vaccine candidate

Malaria transmission-blocking vaccines (TBV) target sexual stage parasites that are transmitted to mosquitoes and critical for spread of the pathogen. The clinically most advanced TBV candidate contains part of the Pro-domain (Pro) and Domain 1 (D1) of Plasmodium falciparum surface protein Pfs230. Subunit vaccines that contain other domains of Pfs230 have so far failed to induce functional antibodies. Here, we produced eight single domain fragments of Pfs230 in Drosophila melanogaster S2 cells and assessed their immunogenicity in mouse immunizations. In addition to D1-specific antibodies, antibodies raised against Domain 12 (D12) showed strong recognition of Pfs230 on the surface of female parasites. Importantly, D12-specific antibodies showed strong functional transmission-reducing activity in membrane feeding assays with cultured parasites, an activity that was complement-dependent. Murine D12-specific antibodies further reduced mosquito transmission of parasites acquired from naturally infected parasite carriers. The D12 antigen was recognized by sera from an all-age cohort of individuals who had been naturally exposed to Plasmodium falciparum with antibody levels increasing with age. In conclusion, we identified Pfs230D12 as a promising new TBV candidate. Impact statementPfs230 Domain 12 induces antibodies in mice that strongly reduce transmission of lab-cultured and naturally circulating malaria parasites to mosquitoes.

immunology↗