A5032544998- Malaria Research and Control
- Mosquito-borne diseases and control
- Complement system in diseases
- HIV Research and Treatment
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- vaccines and immunoinformatics approaches
- Parasites and Host Interactions
- Gut microbiota and health
- Global Maternal and Child Health
- Invertebrate Immune Response Mechanisms
- Clostridium difficile and Clostridium perfringens research
- Immune responses and vaccinations
- Hepatitis B Virus Studies
- Parasite Biology and Host Interactions
- Diverse Scientific Research Studies
- Travel-related health issues
- Zoonotic diseases and public health
- Computational Drug Discovery Methods
- Hemoglobinopathies and Related Disorders
- Urological Disorders and Treatments
- Dietary Effects on Health
- Pregnancy and preeclampsia studies
- Iron Metabolism and Disorders
Université des Sciences, des Techniques et des Technologies de Bamako
2016-2025
University of Bamako
2009-2024
National Institute of Allergy and Infectious Diseases
2024
National Institutes of Health
2022-2024
Frederick National Laboratory for Cancer Research
2024
Mali-Folkecenter
2014-2024
Karolinska Institutet
2010-2015
University of the Sciences
2013-2015
University of California, Irvine
2015
Epidemiological observations in malaria endemic areas have long suggested a deficiency the generation and maintenance of B cell memory to Plasmodium falciparum (Pf) individuals chronically reinfected with parasite. Recently, functionally phenotypically distinct population FCRL4(+) hyporesponsive cells (MBCs) was reported be expanded HIV-infected high viral loads. In this study, we provide evidence that similar atypical MBC is significantly Pf-exposed Malian adults children as young 2 years...
Abs are central to malaria immunity, which is only acquired after years of exposure Plasmodium falciparum ( Pf ). Despite the enormous worldwide burden malaria, targets protective and basis their inefficient acquisition unknown. Addressing these knowledge gaps could accelerate vaccine development. To this end, we developed a protein microarray containing ∼23% 5,400-protein proteome used array probe plasma from 220 individuals between ages 2–10 18–25 in Mali before 6-month season. Episodes...
Protective antibodies in Plasmodium falciparum malaria are only acquired after years of repeated infections. Chronic exposure is associated with a large increase atypical memory B cells (MBCs) that resemble expanded variety persistent viral Understanding the function MBCs and their relationship to classical will be critical developing effective vaccines for other chronic We show VH gene repertoires somatic hypermutation rates indistinguishable indicating common developmental history....
In experimental models of human and mouse malaria, sterilizing liver stage immunity that blocks progression Plasmodium infection to the symptomatic blood can be readily demonstrated. However, it remains unclear whether individuals in malaria-endemic areas acquire such immunity.In Mali, 251 healthy children adults aged 4-25 years who were free blood-stage by polymerase chain reaction (PCR) enrolled a longitudinal study just prior an intense 6-month malaria season. Subsequent clinical episodes...
Malaria-specific antibody responses are short lived in children, leaving them susceptible to repeated bouts of febrile malaria. The cellular and molecular mechanisms underlying this apparent immune deficiency poorly understood. Recently, T follicular helper (Tfh) cells have been shown play a critical role generating long-lived responses. We show that Malian children resting PD-1+CXCR5+CD4+ Tfh circulation resemble germinal center phenotypically functionally. Within population,...
CIS43LS is a monoclonal antibody that was shown to protect against controlled Plasmodium falciparum infection in phase 1 clinical trial. Whether can prevent P. region which the endemic unknown.We conducted 2 trial assess safety and efficacy of single intravenous infusion healthy adults Mali over 6-month malaria season. In Part A, assessed at three escalating dose levels. B, participants were randomly assigned (in 1:1:1 ratio) receive 10 mg per kilogram body weight, 40 kilogram, or placebo....
BackgroundSubcutaneous administration of the monoclonal antibody L9LS protected adults against controlled Plasmodium falciparum infection in a phase 1 trial. Whether administered subcutaneously can protect children from P. region where this organism is endemic unclear.MethodsWe conducted 2 trial Mali to assess safety and efficacy subcutaneous 6 10 years age over 6-month malaria season. In part A trial, was assessed at three dose levels adults, followed by assessment two children. B were...
The most advanced monoclonal antibodies (mAbs) and vaccines against malaria target the central repeat region or closely related sequences within Plasmodium falciparum circumsporozoite protein (PfCSP). Here, using an antigen-agnostic strategy to investigate human antibody responses whole sporozoites, we identified a class of mAbs that cryptic PfCSP epitope is only exposed after cleavage subsequent pyroglutamylation (pGlu) newly formed N terminus. This pGlu-CSP not targeted by current...
Immunity to Plasmodium falciparum (Pf) malaria is only acquired after years of repeated infections and wanes rapidly without ongoing parasite exposure. Antibodies are central immunity, yet little known about the B-cell biology that underlies inefficient acquisition Pf-specific humoral immunity. This year-long prospective study in Mali 185 individuals aged 2 25 shows memory B-cells antibodies gradually a stepwise fashion over Pf Both B cells antibody titers increased acute then, six months...
In malaria-naïve individuals, Plasmodium falciparum infection results in high levels of parasite-infected red blood cells (iRBCs) that trigger systemic inflammation and fever. Conversely, individuals endemic areas who are repeatedly infected often asymptomatic have low iRBCs, even young children. We hypothesized febrile malaria alters the immune system such P. re-exposure reduced production pro-inflammatory cytokines/chemokines enhanced anti-parasite effector responses compared to induced...
Background. Plasmodium falciparum reticulocyte-binding protein homologue 5 (PfRH5) is a blood-stage parasite essential for host erythrocyte invasion. PfRH5-specific antibodies raised in animals inhibit growth vitro, but the relevance of naturally acquired humans unclear.
Identifying molecular predictors and mechanisms of malaria disease is important for understanding how Plasmodium falciparum controlled. Transcriptomic studies in humans have so far been limited to retrospective analysis blood samples from clinical cases. In this prospective, proof-of-principle study, we compared whole-blood RNA-seq profiles at pre-and post-infection time points Malian adults who were either asymptomatic (n = 5) or febrile 3) during their first seasonal PCR-positive P....
In malaria-naïve children and adults, Plasmodium falciparum -infected red blood cells ( Pf -iRBCs) trigger fever other symptoms of systemic inflammation. However, in endemic areas where individuals experience repeated infections over many years, the risk -iRBC-triggered inflammatory decreases with cumulative exposure. The molecular mechanisms underlying these clinical observations remain unclear. Age-stratified analyses uninfected, asymptomatic Malian before malaria season revealed that...
Malaria during pregnancy contributes to maternal anemia and low birth weight. In East Africa, several studies have demonstrated that intermittent preventive treatment (IPT) with sulfadoxine-pyrimethamine (SP) is more efficacious than weekly chloroquine (CQ) chemoprophylaxis in preventing these adverse consequences. To our knowledge, there are no published trials evaluating IPT West Africa.We undertook a randomized controlled trial of CQ chemoprophylaxis, 2-dose CQ, SP; 1163 women were...
The World Health Organization (WHO) recently recommended that the time to first malaria episode serve as primary end point in phase III vaccine trials--the of which will be held Africa. Although common red blood cell (RBC) polymorphisms such sickle hemoglobin (HbS) are known protect against Africa, their impact on this has not been investigated.A longitudinal study 225 individuals aged 2-25 years was conducted Mali. association between RBC and evaluated.Among children 2-10 years, trait...
Background Antibodies that protect against Plasmodium falciparum (Pf) malaria are only acquired after years of repeated infections. The B cell biology underlies this observation is poorly understood. We previously reported "atypical" memory cells increased in children and adults exposed to intense Pf transmission Mali, similar what has been observed individuals infected with HIV. In study we examined subsets -infected Peru Mali determine if intensity correlates atypical expansion....
Chronic asymptomatic Plasmodium falciparum infections are common in endemic areas and thought to contribute the maintenance of malaria immunity. Whether treatment these increases subsequent risk clinical episodes is unclear.In a 3-year study Mali, individuals with or without P. infection at end 6-month dry season were identified by polymerase chain reaction (PCR), was compared during ensuing transmission season. At second season, 3 groups children identified: (1) infected as detected rapid...
IgG antibodies play a role in malaria immunity, but whether and how IgM protects from the biology of Plasmodium falciparum (Pf)–specific B cells is unclear. In Mali cohort spanning infants to adults, we conducted longitudinal analyses Pf- influenza-specific cells. We found that Pf-specific memory (MBCs) are disproportionally IgM+ only gradually shift IgG+ with age, contrast MBCs predominantly infancy adulthood. cell receptor analysis showed somatically hypermutated at levels comparable...
Several infectious and autoimmune diseases are associated with an expansion of CD21 − CD27 atypical B cells (atBCs) that up-regulate inhibitory receptors exhibit altered cell receptor (BCR) signaling. The function atBCs remains unclear, few studies have investigated the biology pathogen-specific during acute infection. Here, we performed longitudinal flow cytometry analyses RNA sequencing Plasmodium falciparum ( Pf )–specific isolated from study participants before shortly after febrile...
Plasmodium falciparum reticulocyte-binding protein homolog 5 (RH5) is the most advanced blood-stage malaria vaccine candidate and being evaluated for efficacy in endemic regions, emphasizing need to study underlying antibody response RH5 during natural infection, which could augment or counteract responses vaccination. Here, we found that RH5-reactive B cells were rare, circulating immunoglobulin G (IgG) short-lived malaria-exposed Malian individuals, despite repeated infections over...
(See the article by Harrington et al, on pages 224–230, and editorial commentary Lake Taylor, 231–233.) Background. In 2003, Mali introduced intermittent preventive therapy in pregnancy (ITPp) with sulfadoxine-pyrimethamine (SP) for control of malaria pregnancy, consisting 2 doses SP given 2nd 3rd trimester. This widely used regimen, although very effective, leaves many women unprotected from during last 4-to-8 weeks gestation, which is a pivotal period fetal weight gain. The aim study was...