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.

Preclinical development of a stabilized RH5 virus-like particle vaccine that induces improved antimalarial antibodies.

Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage malaria vaccine antigen target, currently in a phase 2b clinical trial as a full-length soluble protein/adjuvant vaccine candidate called RH5.1/Matrix-M. We identify that disordered regions of the full-length RH5 molecule induce non-growth inhibitory antibodies in human vaccinees and that a re-engineered and stabilized immunogen (including just the alpha-helical core of RH5) induces a qualitatively superior growth inhibitory antibody response in rats vaccinated with this protein formulated in Matrix-M adjuvant.

Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex.

Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric "RCR-complex". We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically.

"I'm not going to do it alone": A qualitative study of barriers to sexual assault service-seeking among college students.

To understand barriers to seeking post-sexual assault services for students of color and lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ+) students. Qualitative interviews about campus and community resources for sexual and relationship violence were conducted with 29 undergraduate and graduate students who held diverse sexual, gender, and racial identities ( = 15 disclosed violence-related service-seeking). Organized within trauma-informed care pillars, thematic coding revealed aspects of campus environment/culture that prevent students from accessing support including challenges identifying experiences as violence; limited cultural and identity-affirming care; limited clarity about resources; confidentiality concerns; difficulty accessing resources; and navigating resources alone.

Safety, tolerability, and Plasmodium falciparum transmission-reducing activity of monoclonal antibody TB31F: a single-centre, open-label, first-in-human, dose-escalation, phase 1 trial in healthy malaria-naive adults.

Background: Malaria elimination requires interruption of the highly efficient transmission of Plasmodium parasites by mosquitoes. TB31F is a humanised monoclonal antibody that binds the gamete surface protein Pfs48/45 and inhibits fertilisation, thereby preventing further parasite development in the mosquito midgut and onward transmission. We aimed to evaluate the safety and efficacy of TB31F in malaria-naive participants.

Comparative Effect of 22 Dietary Sources of Fiber on Gut Microbiota of Healthy Humans .

Human gut microbiota has a fundamental role in human health, and diet is one of the most relevant factors modulating the gut microbial ecosystem. Fiber, fat, proteins, and micronutrients can shape microbial activity and structure. Much information is available on the role of defined prebiotic fibers on gut microbiota, but less known are the effects of intact dietary fiber sources on healthy gut ecosystems.

Author Correction: Tropical forest soil carbon stocks do not increase despite 15 years of doubled litter inputs.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Interacting with Members of the Public to Discuss the Impact of Food Choices on Climate Change-Experiences from Two UK Public Engagement Events.

Food systems contribute to up to 37% of global greenhouse gas emissions, and emissions are increasing. Since the emissions vary greatly between different foods, citizens' choices can make a big difference to climate change. Public engagement events are opportunities to communicate these complex issues: to raise awareness about the impact of citizens' own food choices on climate change and to generate support for changes in all food system activities, the food environment and food policy.

An open-label phase 1/2a trial of a genetically modified rodent malaria parasite for immunization against malaria.

For some diseases, successful vaccines have been developed using a nonpathogenic counterpart of the causative microorganism of choice. The nonpathogenicity of the rodent () parasite in humans prompted us to evaluate its potential as a platform for vaccination against human infection by (), a causative agent of malaria. We hypothesized that the genetic insertion of a leading protein target for clinical development of a malaria vaccine, circumsporozoite protein (CSP), in its natural pre-erythrocytic environment, would enhance 's capacity to induce protective immunity against infection.

Tropical forest soil carbon stocks do not increase despite 15 years of doubled litter inputs.

Soil organic carbon (SOC) dynamics represent a persisting uncertainty in our understanding of the global carbon cycle. SOC storage is strongly linked to plant inputs via the formation of soil organic matter, but soil geochemistry also plays a critical role. In tropical soils with rapid SOC turnover, the association of organic matter with soil minerals is particularly important for stabilising SOC but projected increases in tropical forest productivity could trigger feedbacks that stimulate the release of stored SOC.

Combining antimalarial drugs and vaccine for malaria elimination campaigns: a randomized safety and immunogenicity trial of RTS,S/AS01 administered with dihydroartemisinin, piperaquine, and primaquine in healthy Thai adult volunteers.

: RTS,S/AS01 is currently the most advanced malaria vaccine but provides incomplete, short-term protection. It was developed for use within the expanded program on immunizations (EPI) for African children. Another use could be adding mass RTS,S/AS01 vaccination to the integrated malaria elimination strategy in the Greater Mekong Subregion (GMS), where multidrug-resistant strains have emerged and spread.

Expression of full-length Plasmodium falciparum P48/45 in P. berghei blood stages: A method to express and evaluate vaccine antigens.

The transmission-blocking vaccine candidate Pfs48/45 from the human malaria parasite Plasmodium falciparum is known to be difficult to express in heterologous systems, either as full-length protein or as correctly folded protein fragments that retain conformational epitopes. In this study we express full-length Pfs48/45 in the rodent parasite P. berghei.

Distinct responses of soil respiration to experimental litter manipulation in temperate woodland and tropical forest.

Global change is affecting primary productivity in forests worldwide, and this, in turn, will alter long-term carbon (C) sequestration in wooded ecosystems. On one hand, increased primary productivity, for example, in response to elevated atmospheric carbon dioxide (CO ), can result in greater inputs of organic matter to the soil, which could increase C sequestration belowground. On other hand, many of the interactions between plants and microorganisms that determine soil C dynamics are poorly characterized, and additional inputs of plant material, such as leaf litter, can result in the mineralization of soil organic matter, and the release of soil C as CO during so-called "priming effects".

Malaria Derived Glycosylphosphatidylinositol Anchor Enhances Anti-Pfs25 Functional Antibodies That Block Malaria Transmission.

Malaria, one of the most common vector borne human diseases, is a major world health issue. In 2015 alone, more than 200 million people were infected with malaria, out of which, 429 000 died. Even though artemisinin-based combination therapies (ACT) are highly effective at treating malaria infections, novel efforts toward development of vaccines to prevent transmission are still needed.

The Automated Root Exudate System (ARES): a method to apply solutes at regular intervals to soils in the field.

Root exudation is a key component of nutrient and carbon dynamics in terrestrial ecosystems. Exudation rates vary widely by plant species and environmental conditions, but our understanding of how root exudates affect soil functioning is incomplete, in part because there are few viable methods to manipulate root exudates . To address this, we devised the Automated Root Exudate System (ARES), which simulates increased root exudation by applying small amounts of labile solutes at regular intervals in the field.

Vaccines to Accelerate Malaria Elimination and Eventual Eradication.

Remarkable progress has been made in coordinated malaria control efforts with substantial reductions in malaria-associated deaths and morbidity achieved through mass administration of drugs and vector control measures including distribution of long-lasting insecticide-impregnated bednets and indoor residual spraying. However, emerging resistance poses a significant threat to the sustainability of these interventions. In this light, the malaria research community has been charged with the development of a highly efficacious vaccine to complement existing malaria elimination measures.

Fractional Third and Fourth Dose of RTS,S/AS01 Malaria Candidate Vaccine: A Phase 2a Controlled Human Malaria Parasite Infection and Immunogenicity Study.

Background: Three full doses of RTS,S/AS01 malaria vaccine provides partial protection against controlled human malaria parasite infection (CHMI) and natural exposure. Immunization regimens, including a delayed fractional third dose, were assessed for potential increased protection against malaria and immunologic responses.

Methods: In a phase 2a, controlled, open-label, study of healthy malaria-naive adults, 16 subjects vaccinated with a 0-, 1-, and 2-month full-dose regimen (012M) and 30 subjects who received a 0-, 1-, and 7-month regimen, including a fractional third dose (Fx017M), underwent CHMI 3 weeks after the last dose.

Healthy Eating Index-2010 and food groups consumed by US adults who meet or exceed fiber intake recommendations NHANES 2001-2010.

Background: The proportion of the US adult population who meet fiber intake recommendations is very low. Information about food groups consumed and diet quality for the adults who consume recommended amounts of fiber are scarce.

Objective: To examine food groups consumed and Healthy Eating Index (HEI-2010) scores for US adults meeting the fiber adequate intake (AI) based on National Health and Nutrition Examination Survey (NHANES) data 2001-2010.

Status of vaccine research and development of vaccines for malaria.

Despite recent progress in reducing deaths attributable to malaria, it continues to claim approximately 500,000 lives per year and is associated with approximately 200 million infections. New tools, including safe and effective vaccines, are needed to ensure that the gains of the last 15 years are leveraged toward achieving the ultimate goal of malaria parasite eradication. In 2015, the European Medicines Agency announced the adoption of a positive opinion for the malaria vaccine candidate most advanced in development, RTS,S/AS01, which provides modest protection against clinical malaria; in early 2016, WHO recommended large-scale pilot implementations of RTS,S in settings of moderate-to-high malaria transmission.

Effects of Cereal, Fruit and Vegetable Fibers on Human Fecal Weight and Transit Time: A Comprehensive Review of Intervention Trials.

Cereal fibers are known to increase fecal weight and speed transit time, but far less data are available on the effects of fruits and vegetable fibers on regularity. This study provides a comprehensive review of the impact of these three fiber sources on regularity in healthy humans. We identified English-language intervention studies on dietary fibers and regularity and performed weighted linear regression analyses for fecal weight and transit time.

Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.

Background: A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use.

Methods: We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI) of VMP001 formulated in the GSK Adjuvant System AS01B.

Demonstration of the Blood-Stage Plasmodium falciparum Controlled Human Malaria Infection Model to Assess Efficacy of the P. falciparum Apical Membrane Antigen 1 Vaccine, FMP2.1/AS01.

Background: Models of controlled human malaria infection (CHMI) initiated by mosquito bite have been widely used to assess efficacy of preerythrocytic vaccine candidates in small proof-of-concept phase 2a clinical trials. Efficacy testing of blood-stage malaria parasite vaccines, however, has generally relied on larger-scale phase 2b field trials in malaria-endemic populations. We report the use of a blood-stage P.

A comparison of Plasmodium falciparum circumsporozoite protein-based slot blot and ELISA immuno-assays for oocyst detection in mosquito homogenates.

Background: The infectivity of Plasmodium gametocytes is typically determined by microscopically examining the midguts of mosquitoes that have taken a blood meal containing potentially infectious parasites. Such assessments are required for the development and evaluation of transmission-reducing interventions (TRI), but are limited by subjectivity, technical complexity and throughput. The detection of circumsporozoite protein (CSP) by enzyme-linked immunosorbent assay (ELISA) and enhanced chemiluminescent slot-blot (ECL-SB) may be used as objective, scalable alternatives to microscopy for the determination of infection prevalence.