Protective antibodies target cryptic epitope unmasked by cleavage of malaria sporozoite protein.

The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within the circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses to whole sporozoites, we identified a class of mAbs that target a cryptic PfCSP epitope that is only exposed after cleavage and subsequent pyroglutamylation (pGlu) of the newly formed N terminus. This pGlu-CSP epitope is not targeted by current anti-PfCSP mAbs and is not included in the licensed malaria vaccines.

Potent AMA1-specific human monoclonal antibody against Plasmodium vivax Pre-erythrocytic and Blood Stages.

New therapeutics are necessary for preventing Plasmodium vivax malaria due to easy transmissibility and dormancy in the liver that increases the clinical burden due to recurrent relapse. In this manuscript we characterize 12 Pv Apical Membrane Antigen 1 (PvAMA1) specific human monoclonal antibodies from Peripheral Blood Mononuclear Cells of a Pv-exposed individual. PvAMA1 is essential for sporozoite and merozoite invasion, making it a unique therapeutic target.

A Global Perspective on Socioeconomic Determinants of Cardiovascular Health.

Cardiovascular disease (CVD) is the leading cause of mortality in the world. From 2005 to 2008, the World Health Organization (WHO) planned an initiative to reduce the mortality rate of CVD by 2030 by addressing health, finance, transport, education, and agriculture in these communities. Plans were underway by many countries to meet the goals of the WHO initiative.

Analysis of the diverse antigenic landscape of the malaria protein RH5 identifies a potent vaccine-induced human public antibody clonotype.

The highly conserved and essential Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has emerged as the leading target for vaccines against the disease-causing blood stage of malaria. However, the features of the human vaccine-induced antibody response that confer highly potent inhibition of malaria parasite invasion into red blood cells are not well defined. Here, we characterize 236 human IgG monoclonal antibodies, derived from 15 donors, induced by the most advanced PfRH5 vaccine.

3-Position Biaryl Endochin-like Quinolones with Enhanced Antimalarial Performance.

ELQ-300 is a potent antimalarial drug with activity against blood, liver, and vector stages of the disease. A prodrug, , exhibits reduced crystallinity and improved in vivo efficacy in preclinical testing, and currently, it is in the developmental pipeline for once-a-week dosing for oral prophylaxis against malaria. Because of the high cost of developing a new drug for human use and the high risk of drug failure, it is prudent to have a back-up plan in place.

Predicting first time depression onset in pregnancy: applying machine learning methods to patient-reported data.

Purpose: To develop a machine learning algorithm, using patient-reported data from early pregnancy, to predict later onset of first time moderate-to-severe depression.

Methods: A sample of 944 U.S.

Potent AMA1-specific human monoclonal antibody against P. vivax Pre-erythrocytic and Blood Stages.

New therapeutics are necessary for preventing Plasmodium vivax malaria due to easy transmissibility and dormancy in the liver that increases the clinical burden due to recurrent relapse. We isolated 12 Pv Apical Membrane Antigen 1 (PvAMA1) specific human monoclonal antibodies from Peripheral Blood Mononuclear Cells of a Pv exposed individual. PvAMA1 is essential for sporozoite and merozoite invasion, making it a unique therapeutic target.

Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine.

Malaria, caused by Plasmodium parasites, remains one of the most devastating infectious diseases worldwide, despite control efforts to lower morbidity and mortality. Both advanced candidate vaccines, RTS,S and R21, are subunit (SU) vaccines that target a single Plasmodium falciparum (Pf) pre-erythrocytic (PE) sporozoite (spz) surface protein known as circumsporozoite (CS). These vaccines induce humoral immunity but fail to elicit CD8 + T-cell responses sufficient for long-term protection.

One hundred and six years of change in a Sonoran Desert plant community: Impact of climate anomalies and trends in species sensitivities.

A major restriction in predicting plant community response to future climate change is a lack of long-term data needed to properly assess species and community response to climate and identify a baseline to detect climate anomalies. Here, we use a 106-year dataset on a Sonoran Desert plant community to test the role of extreme temperature and precipitation anomalies on community dynamics at the decadal scale and over time. Additionally, we tested the climate sensitivity of 39 desert plant species and whether sensitivity was associated with growth form, longevity, geographic range, or local dominance.

Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine.

Malaria, caused parasites, remains one of the most devastating infectious diseases worldwide, despite control efforts that have lowered morbidity and mortality. The only vaccine candidates to show field efficacy are those targeting the asymptomatic pre-erythrocytic (PE) stages of infection. The subunit (SU) RTS,S/AS01 vaccine, the only licensed malaria vaccine to date, is only modestly effective against clinical malaria.

Accelerated prime-and-trap vaccine regimen in mice using repRNA-based CSP malaria vaccine.

Malaria, caused by parasites, remains one of the most devastating infectious diseases worldwide, despite control efforts that have lowered morbidity and mortality. The only vaccine candidates to show field efficacy are those targeting the asymptomatic pre-erythrocytic (PE) stages of infection. The subunit (SU) RTS,S/AS01 vaccine, the only licensed malaria vaccine to date, is only modestly effective against clinical malaria.

Development of risk prediction models for preterm delivery in a rural setting in Ethiopia.

Background: Preterm birth complications are the leading causes of death among children under five years. However, the inability to accurately identify pregnancies at high risk of preterm delivery is a key practical challenge, especially in resource-constrained settings with limited availability of biomarkers assessment.

Methods: We evaluated whether risk of preterm delivery can be predicted using available data from a pregnancy and birth cohort in Amhara region, Ethiopia.

Creation and preclinical evaluation of genetically attenuated malaria parasites arresting growth late in the liver.

Whole-sporozoite (WSp) malaria vaccines induce protective immune responses in animal malaria models and in humans. A recent clinical trial with a WSp vaccine comprising genetically attenuated parasites (GAP) which arrest growth early in the liver (PfSPZ-GA1), showed that GAPs can be safely administered to humans and immunogenicity is comparable to radiation-attenuated PfSPZ Vaccine. GAPs that arrest late in the liver stage (LA-GAP) have potential for increased potency as shown in rodent malaria models.

Marine subsidies produce cactus forests on desert islands.

In island systems, nitrogen-rich seabird guano is a marine subsidy that can shape terrestrial plant communities. In zones of nutrient upwelling such as the Gulf of California, copious seabird guano is commonplace on bird islands. Several bird islands host regionally unique cactus forests, especially of the large columnar cactus, cardón (Pachycereus pringlei).

Anti-TRAP/SSP2 monoclonal antibodies can inhibit sporozoite infection and may enhance protection of anti-CSP monoclonal antibodies.

Vaccine-induced sterilizing protection from infection by Plasmodium parasites, the pathogens that cause malaria, will be essential in the fight against malaria as it would prevent both malaria-related disease and transmission. Stopping the relatively small number of parasites injected by the mosquito before they can migrate from the skin to the liver is an attractive means to this goal. Antibody-eliciting vaccines have been used to pursue this objective by targeting the major parasite surface protein present during this stage, the circumsporozoite protein (CSP).

Malaria vaccine trial shows the potentiating power of incremental progress.

The complexity of malaria has precluded many "slam dunk" attempts at a vaccine. In this issue, Minassian et al. present efficacy trial results that demonstrate progress for a much-anticipated malaria vaccine candidate and pave the way to future iterations by validating a comprehensive vaccine development framework.

Monoclonal antibodies for malaria prevention.

Monoclonal antibodies are highly specific proteins that are cloned from a single B cell and bind to a single epitope on a pathogen. These laboratory-made molecules can serve as prophylactics or therapeutics for infectious diseases and have an impressive capacity to modulate the progression of disease, as demonstrated for the first time on a large scale during the COVID-19 pandemic. The high specificity and natural starting point of monoclonal antibodies afford an encouraging safety profile, yet the high cost of production remains a major limitation to their widespread use.

Integrating Earth-life systems: a geogenomic approach.

For centuries, scientists have recognized and worked to understand how Earth's mutable landscape and climate shape the distribution and evolution of species. Here, we describe the emerging field of geogenomics, which uses the reciprocal and deep integration of geologic, climatic, and population genomic data to define and test cause-effect relationships between Earth and life at intermediate spatial and temporal scales (i.e.

A Peer-Led, Artificial Intelligence-Augmented Social Network Intervention to Prevent HIV Among Youth Experiencing Homelessness.

Background: Youth experiencing homelessness (YEH) are at elevated risk of HIV/AIDS and disproportionately identify as racial, ethnic, sexual, and gender minorities. We developed a new peer change agent (PCA) HIV prevention intervention with 3 arms: (1) an arm using an artificial intelligence (AI) planning algorithm to select PCAs; (2) a popularity arm, the standard PCA approach, operationalized as highest degree centrality (DC); and (3) an observation-only comparison group.

Setting: A total of 713 YEH were recruited from 3 drop-in centers in Los Angeles, CA.

Platelet derived growth factor receptor β (PDGFRβ) is a host receptor for the human malaria parasite adhesin TRAP.

Following their inoculation by the bite of an infected Anopheles mosquito, the malaria parasite sporozoite forms travel from the bite site in the skin into the bloodstream, which transports them to the liver. The thrombospondin-related anonymous protein (TRAP) is a type 1 transmembrane protein that is released from secretory organelles and relocalized on the sporozoite plasma membrane. TRAP is required for sporozoite motility and host infection, and its extracellular portion contains adhesive domains that are predicted to engage host receptors.

Accurate dosimetric measurement of large extended SSD fields for comparison to TPS models.

Purpose: There is little evidence in the literature which quantifies the accuracy of Treatment Planning Systems (TPSs) using large fields at extended SSD (eSSD). This paper introduces the approach taken at Christchurch Hospital, New Zealand to validate the use of the Monaco TPS for Total Body Irradiation (TBI) treatments.

Methods: A purpose-built device for allowing precise movements of block-like phantoms called a Phantom Mobility Device (PMD) was used for collecting measurements at eSSD.

Generation of a Genetically Modified Chimeric Parasite Expressing Circumsporozoite Protein for Malaria Vaccine Development.

Chimeric rodent malaria parasites with the endogenous circumsporozoite protein () gene replaced with from the human parasites () and () are used in preclinical evaluation of CSP vaccines. Chimeric rodent parasites expressing CSP have also been assessed as whole sporozoite (WSP) vaccines. Comparable chimeric parasites expressing CSP of could be used both for clinical evaluation of vaccines targeting CSP in controlled human infections and in WSP vaccines targeting and .