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 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 (MSP1) induced antibodies that mediated Fc-IgG functional activity in five independent assays. We found that anti-MSP1 antibodies induced complement fixation via C1q, monocyte-mediated phagocytosis, neutrophil respiratory burst, and natural killer cell degranulation as well as IFNγ production.

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.

Anti-merozoite antibodies induce natural killer cell effector function and are associated with immunity against malaria.

Natural killer (NK) cells are potent immune effectors that can be activated via antibody-mediated Fc receptor engagement. Using multiparameter flow cytometry, we found that NK cells degranulate and release IFN-γ upon stimulation with antibody-opsonized merozoites. Antibody-dependent NK (Ab-NK) activity was largely strain transcending and enhanced invasion inhibition into erythrocytes.

Socioeconomic differences in animal food consumption: Education rather than income makes a difference.

Background/aims: Evidence points toward more sustainable and health-conscious dietary behaviors among individuals with higher socioeconomic status. However, these differences vary considerably depending on which indicator of socioeconomic status is examined. Here, we present a systematic parallel investigation of multiple indicators of socioeconomic status as predictors of animal food consumption frequency and selected food-related behaviors in Germany.

Phagocytosis of Plasmodium falciparum ring-stage parasites predicts protection against malaria.

Ring-infected erythrocytes are the predominant asexual stage in the peripheral circulation but are rarely investigated in the context of acquired immunity against Plasmodium falciparum malaria. Here we compare antibody-dependent phagocytosis of ring-infected parasite cultures in samples from a controlled human malaria infection (CHMI) study (NCT02739763). Protected volunteers did not develop clinical symptoms, maintained parasitaemia below a predefined threshold of 500 parasites/μl and were not treated until the end of the study.

The impact of lockdowns during the COVID-19 pandemic on work-related accidents in Austria in 2020.

Background: This study aims to investigate the impact of the lockdowns during the COVID-19 (Corona-Virus-Disease 19) pandemic in Austria on work-related accidents in the year 2020. Apart from the lockdowns, multiple work-related measures were introduced in 2020, such as the new law on short-term work and regulation on accidents during home-office. Their combined effects on work-related accidents are unknown and a secondary parameter of this study.

BCG Provides Short-Term Protection from Experimental Cerebral Malaria in Mice.

Clinical and experimental evidence suggests that the tuberculosis vaccine BCG offers protection against unrelated pathogens including the malaria parasite. Cerebral malaria (CM) is the most severe complication associated with infection in humans and is responsible for most of the fatalities attributed to malaria. We investigated whether BCG protected C57BL/6 mice from ANKA (PbA)-induced experimental CM (ECM).

A leopard never changes its spots: Development of colonic adenocarcinoma in an Indiana Pouch.

Colonic adenocarcinoma of a urinary diversion is rare. We report a case of a 70 year-old woman who developed such a malignancy 12 years after creation of an Indiana pouch urinary diversion for treatment of urothelial carcinoma of the bladder cancer.

KILchip v1.0: A Novel Merozoite Protein Microarray to Facilitate Malaria Vaccine Candidate Prioritization.

Passive transfer studies in humans clearly demonstrated the protective role of IgG antibodies against malaria. Identifying the precise parasite antigens that mediate immunity is essential for vaccine design, but has proved difficult. Completion of the genome revealed thousands of potential vaccine candidates, but a significant bottleneck remains in their validation and prioritization for further evaluation in clinical trials.

Transmission of the malaria parasite requires ferlin for gamete egress from the red blood cell.

Ferlins mediate calcium-dependent vesicular fusion. Although conserved throughout eukaryotic evolution, their function in unicellular organisms including apicomplexan parasites is largely unknown. Here, we define a crucial role for a ferlin-like protein (FLP) in host-to-vector transmission of the rodent malaria parasite Plasmodium berghei.

A Cross-Stage Antigen Contributes to the Development of Experimental Cerebral Malaria.

Cerebral malaria is a complex neurological syndrome caused by an infection with parasites and is exclusively attributed to a series of host-parasite interactions at the pathological blood-stage of infection. In contrast, the preceding intra-hepatic phase of replication is generally considered clinically silent and thereby excluded from playing any role in the development of neurological symptoms. In this study, however, we present an antigen maLS_05 that is presented to the host immune system by both pre-erythrocytic and intra-erythrocytic stages and contributes to the development of cerebral malaria in mice.

Varying Immunizations With Radiation-Attenuated Sporozoites Alter Tissue-Specific CD8 T Cell Dynamics.

Whole sporozoite vaccines represent one of the most promising strategies to induce protection against malaria. However, the development of efficient vaccination protocols still remains a major challenge. To understand how the generation of immunity is affected by variations in vaccination dosage and frequency, we systematically analyzed intrasplenic and intrahepatic CD8 T cell responses following varied immunizations of mice with radiation-attenuated sporozoites.

Protection from experimental cerebral malaria with a single intravenous or subcutaneous whole-parasite immunization.

Cerebral malaria is a life-threatening complication of Plasmodia infection and a major cause of child mortality in Sub-Saharan Africa. We report that protection from experimental cerebral malaria in the rodent model is obtained by a single intravenous or subcutaneous whole-parasite immunization. Whole-parasite immunization with radiation-attenuated sporozoites was equally protective as immunization with non-attenuated sporozoites under chemoprophylaxis.

Plasmodium attenuation: connecting the dots between early immune responses and malaria disease severity.

Sterile attenuation of Plasmodium parasites at the liver-stage either by irradiation or genetic modification, or at the blood-stage by chemoprophylaxis, has been shown to induce immune responses that can protect against subsequent wild-type infection. However, following certain interventions, parasite attenuation can be incomplete or non-sterile. Instead parasites are rendered developmentally stunted but still capable of establishing an acute infection.

Proteomic analysis of the Plasmodium male gamete reveals the key role for glycolysis in flagellar motility.

Background: Gametogenesis and fertilization play crucial roles in malaria transmission. While male gametes are thought to be amongst the simplest eukaryotic cells and are proven targets of transmission blocking immunity, little is known about their molecular organization. For example, the pathway of energy metabolism that power motility, a feature that facilitates gamete encounter and fertilization, is unknown.