Breadth of Fc-mediated effector function correlates with clinical immunity following human malaria challenge.

Malaria is a life-threatening disease of global health importance, particularly in sub-Saharan Africa. The growth inhibition assay (GIA) is routinely used to evaluate, prioritize, and quantify the efficacy of malaria blood-stage vaccine candidates but does not reliably predict either naturally acquired or vaccine-induced protection. Controlled human malaria challenge studies in semi-immune volunteers provide an unparalleled opportunity to robustly identify mechanistic correlates of protection. We leveraged this platform to undertake a head-to-head comparison of seven functional antibody assays that are relevant to immunity against the erythrocytic merozoite stage of Plasmodium falciparum. Fc-mediated effector functions were strongly associated with protection from clinical symptoms of malaria and exponential parasite multiplication, while the gold standard GIA was not. The breadth of Fc-mediated effector function discriminated clinical immunity following the challenge. These findings present a shift in the understanding of the mechanisms that underpin immunity to malaria and have important implications for vaccine development.

Continuously increasing e-scooter accidents and their possible prevention in a large European city.

PURPOSE: During the last few years, the number of electric scooter (e-scooter) users has risen to an all-time high. This study aimed to analyze e-scooter related accidents and trauma prevention measures in a large European city (Vienna, Austria). METHODS: This retrospective study comprises a thorough data assessment and analysis of all e-scooter related accidents between 2018 and 2021 at a large level 1 trauma center in Vienna. Based on the data analysis, risk factors were identified, and possible prevention strategies were proposed. RESULTS: During the observed period, 1337 patients sustained an injury from an e-scooter. Of these, 1230 were injured directly while driving (92%). The remaining 107 patients (8%) were classified as non-driving injuries. 927 injuries involved males (69.3%). The mean age was 32.1 years (range 4-86 years). Of all injured patients, 429 (32.1%) sustained at least one serious injury. The most common injuries included radial head fractures and concussions. Among the accidents treated, the use of protective equipment was sporadic. For example, helmets were worn in only 13.7% of cases. Wearing a helmet reduced the number of head injuries (24% versus 46.8%). In just three years, the number of patients increased 19-fold with a focus in the summer months. CONCLUSION: This study shows a substantial and sustained increase in e-scooter accidents with potentially serious injuries. Helmet use was found to be an effective form of head injury prevention. Further options for using protective equipment should be evaluated to improve the safety aspects of riding e-scooters.

Full-length MSP1 is a major target of protective immunity after controlled human malaria infection.

The merozoite surface protein 1 (MSP1) is the most abundant protein on the surface of the invasive merozoite stages of Plasmodium falciparum and has long been considered a key target of protective immunity. We used samples from a single controlled human malaria challenge study to test whether the full-length version of MSP1 (MSP1FL) induced antibodies that mediated Fc-IgG functional activity in five independent assays. We found that anti-MSP1FL antibodies induced complement fixation via C1q, monocyte-mediated phagocytosis, neutrophil respiratory burst, and natural killer cell degranulation as well as IFNγ production. Activity in each of these assays was strongly associated with protection. The breadth of MSP1-specific Fc-mediated effector functions was more strongly associated with protection than the individual measures and closely mirrored what we have previously reported using the same assays against merozoites. Our findings suggest that MSP1FL is an important target of functional antibodies that contribute to a protective immune response against malaria.