Whole sporozoite immunization with Plasmodium falciparum strain NF135 in a randomized trial.

Background: Whole sporozoite immunization under chemoprophylaxis (CPS regime) induces long-lasting sterile homologous protection in the controlled human malaria infection model using Plasmodium falciparum strain NF54. The relative proficiency of liver-stage parasite development may be an important factor determining immunization efficacy. Previous studies show that Plasmodium falciparum strain NF135 produces relatively high numbers of large liver-stage schizonts in vitro.

Enhanced vitamin K expenditure as a major contributor to vitamin K deficiency in COVID-19.

Objectives: Vitamin K deficiency consistently associates with worse clinical outcome in COVID-19 patients. However, whether this is due to increased expenditure during inflammation or poor vitamin K status prior to infection remained unknown.

Methods: Dp-ucMGP levels of 128 individuals were measured for the post-MONICA study and were compared to SARS-CoV-2 PCR testing results.

Comment on Kremer et al. Kidney Function-Dependence of Vitamin K-Status Parameters: Results from the TransplantLines Biobank and Cohort Studies. 2021, , 3069.

In the article "Kidney Function-Dependence of Vitamin K-Status Parameters: Results from the TransplantLines Biobank and Cohort Studies", Kremer et al. [..

Corrigendum: Effects of Vitamin D and K on Interleukin-6 in COVID-19.

[This corrects the article DOI: 10.3389/fnut.2021.

Comment on Sobczyk, M.K.; Gaunt, T.R. The Effect of Circulating Zinc, Selenium, Copper and Vitamin K on COVID-19 Outcomes: A Mendelian Randomization Study. 2022, , 233.

Sobczyk and Gaunt genetically predicted circulating zinc, selenium, copper, and vitamin K levels-instead of directly measuring nutrients in blood-and hypothesized that these levels would associate with SARS-CoV-2 infection and COVID-19 severity [...

Effects of Vitamin D and K on Interleukin-6 in COVID-19.

Background: Pathology during COVID-19 infection arises partly from an excessive inflammatory response with a key role for interleukin (IL)-6. Both vitamin D and K have been proposed as potential modulators of this process.

Methods: We assessed vitamin D and K status by measuring circulating 25-hydroxyvitamin D (25(OH)D) and desphospho-uncarboxylated Matrix Gla-Protein (dp-ucMGP), respectively in 135 hospitalized COVID-19 patients in relation to inflammatory response, elastic fiber degradation and clinical outcomes.

Controlled Human Malaria Infection Induces Long-Term Functional Changes in Monocytes.

Innate immune memory responses (also termed "") have been described in monocytes after BCG vaccination and after stimulation with microbial and endogenous ligands such as LPS, β-glucan, oxidized LDL, and monosodium urate crystals. However, whether clinical infections are also capable of inducing a trained immunity phenotype remained uncertain. We evaluated whether infection can induce innate immune memory by measuring monocyte-derived cytokine production from five volunteers undergoing Controlled Human Malaria Infection.

Vitamin K epoxide reductase complex subunit 1 (VKORC1) gene polymorphism as determinant of differences in Covid-19-related disease severity.

Covid-19, caused by SARS-CoV-2, has major world-wide health-related and socio-economic consequences. There are large disparities in the burden of Covid-19 with an apparent lower risk of poor outcomes in East Asians compared to populations in the West. A recent study suggested that Covid-19 leads to a severe extrahepatic vitamin K insufficiency, which could lead to impaired activation of extrahepatic proteins like endothelial anticoagulant protein S in the presence of normal hepatic procoagulant activity.

Vitamin K metabolism as the potential missing link between lung damage and thromboembolism in Coronavirus disease 2019.

Coronavirus disease 2019 (Covid-19), caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2, exerts far-reaching effects on public health and socio-economic welfare. The majority of infected individuals have mild to moderate symptoms, but a significant proportion develops respiratory failure due to pneumonia. Thrombosis is another frequent manifestation of Covid-19 that contributes to poor outcomes.

Reduced Vitamin K Status as a Potentially Modifiable Risk Factor of Severe Coronavirus Disease 2019.

Background: Respiratory failure and thromboembolism are frequent in severe acute respiratory syndrome coronavirus 2-infected patients. Vitamin K activates both hepatic coagulation factors and extrahepatic endothelial anticoagulant protein S, required for thrombosis prevention. In times of vitamin K insufficiency, hepatic procoagulant factors are preferentially activated over extrahepatic proteins.

BCG vaccination in humans inhibits systemic inflammation in a sex-dependent manner.

BACKGROUNDInduction of innate immune memory, also termed trained immunity, by the antituberculosis vaccine bacillus Calmette-Guérin (BCG) contributes to protection against heterologous infections. However, the overall impact of BCG vaccination on the inflammatory status of an individual is not known; while induction of trained immunity may suggest increased inflammation, BCG vaccination has been epidemiologically associated with a reduced incidence of inflammatory and allergic diseases.METHODSWe investigated the impact of BCG (BCG-Bulgaria, InterVax) vaccination on systemic inflammation in a cohort of 303 healthy volunteers, as well as the effect of the inflammatory status on the response to vaccination.

A double-blind, placebo-controlled phase 1/2a trial of the genetically attenuated malaria vaccine PfSPZ-GA1.

Immunization with attenuated sporozoites can induce protection against malaria infection, as shown by (Pf) sporozoites attenuated by radiation in multiple clinical trials. As alternative attenuation strategy with a more homogeneous population of Pf sporozoites (PfSPZ), genetically engineered sporozoites (SPZ) lacking the genes b9 and slarp induced sterile protection against malaria in mice. Consequently, PfSPZ-GA1 Vaccine, a Pf identical double knockout (Pf∆∆), was generated as a genetically attenuated malaria parasite vaccine and tested for safety, immunogenicity, and preliminary efficacy in malaria-naïve Dutch volunteers.

Activatory Receptor NKp30 Predicts NK Cell Activation During Controlled Human Malaria Infection.

Natural killer (NK) cells are known to be activated during malaria infection, exhibiting both cytokine production and cytotoxic functions. However, NK cells are heterogeneous in their expression of surface activatory and inhibitory receptors which may influence their response to malaria parasites. Here, we studied the surface marker profile and activation dynamics of NK cells during a Controlled Human Malaria Infection in 12 healthy volunteers.

Outcomes of controlled human malaria infection after BCG vaccination.

Recent evidence suggests that certain vaccines, including Bacillus-Calmette Guérin (BCG), can induce changes in the innate immune system with non-specific memory characteristics, termed 'trained immunity'. Here we present the results of a randomised, controlled phase 1 clinical trial in 20 healthy male and female volunteers to evaluate the induction of immunity and protective efficacy of the anti-tuberculosis BCG vaccine against a controlled human malaria infection. After malaria challenge infection, BCG vaccinated volunteers present with earlier and more severe clinical adverse events, and have significantly earlier expression of NK cell activation markers and a trend towards earlier phenotypic monocyte activation.

Can Patrolling Liver-Resident T Cells Control Human Malaria Parasite Development?

Recently, a population of non-recirculating, tissue-resident memory CD8 T cells has been identified; cells that seems to act as key sentinels for invading microorganisms with enhanced effector functions. In malaria, the liver represents the first site for parasite development before a definite infection is established in circulating red blood cells. Here, we discuss the evidence obtained from animal models on several diseases and hypothesize that liver-resident memory CD8 T cells (hepatic T) play a critical role in providing protective liver-stage immunity against Plasmodium malaria parasites.

Antibody Responses to Antigenic Targets of Recent Exposure Are Associated With Low-Density Parasitemia in Controlled Human Infections.

The majority of malaria infections in low transmission settings remain undetectable by conventional diagnostics. A powerful model to identify antibody responses that allow accurate detection of recent exposure to low-density infections is controlled human malaria infection (CHMI) studies in which healthy volunteers are infected with the parasite. We aimed to evaluate antibody responses in malaria-naïve volunteers exposed to a single CHMI using a custom-made protein microarray.

Mosquito Infectivity and Parasitemia after Controlled Human Malaria Infection.

Controlled Human Malaria Infection (CHMI) has become an increasingly important tool for the evaluation of drugs and vaccines. Controlled Human Malaria Infection has been demonstrated to be a reproducible model; however, there is some variability in time to onset of parasitemia between volunteers and studies. At our center, mosquitoes infected with by membrane feeding have variable and high salivary gland sporozoite load (mean 78,415; range 26,500-160,500).

Humoral protection against mosquito bite-transmitted infection in humanized mice.

A malaria vaccine that prevents infection will be an important new tool in continued efforts of malaria elimination, and such vaccines are under intense development for the major human malaria parasite (). Antibodies elicited by vaccines can block the initial phases of parasite infection when sporozoites are deposited into the skin by mosquito bite and then target the liver for further development. However, there are currently no standardized in vivo preclinical models that can measure the inhibitory activity of antibody specificities against sporozoite infection via mosquito bite.

Modest heterologous protection after Plasmodium falciparum sporozoite immunization: a double-blind randomized controlled clinical trial.

Background: A highly efficacious vaccine is needed for malaria control and eradication. Immunization with Plasmodium falciparum NF54 parasites under chemoprophylaxis (chemoprophylaxis and sporozoite (CPS)-immunization) induces the most efficient long-lasting protection against a homologous parasite. However, parasite genetic diversity is a major hurdle for protection against heterologous strains.

Infectivity of sporozoites determines emerging parasitemia in infected volunteers.

Malaria sporozoites must first undergo intrahepatic development before a pathogenic blood-stage infection is established. The success of infection depends on host and parasite factors. In healthy human volunteers undergoing controlled human malaria infection (CHMI), we directly compared three clinical isolates for their ability to infect primary human hepatocytes in vitro and to drive the production of blood-stage parasites in vivo.

Erratum to: Diagnosis and treatment based on quantitative PCR after controlled human malaria infection.

[This corrects the article DOI: 10.1186/s12936-016-1434-z.].