Publications by authors named "Daniel G W Alanine"

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.

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Understanding mechanisms of antibody synergy is important for vaccine design and antibody cocktail development. Examples of synergy between antibodies are well-documented, but the mechanisms underlying these relationships often remain poorly understood. The leading blood-stage malaria vaccine candidate, CyRPA, is essential for invasion of Plasmodium falciparum into human erythrocytes.

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Reticulocyte-binding protein homolog 5 (RH5) is a leading blood-stage vaccine candidate. Another possible candidate, apical membrane antigen 1 (AMA1), was not efficacious in malaria-endemic populations, likely due to pre-existing antimalarial antibodies that interfered with the activity of vaccine-induced AMA1 antibodies, as judged by growth inhibition assay (GIA). To determine how pre-existing antibodies interact with vaccine-induced RH5 antibodies, we purify total and RH5-specific immunoglobulin Gs (IgGs) from malaria-exposed Malians and malaria-naive RH5 vaccinees.

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Several laboratories have created rat basophil leukemia (RBL) cell lines stably transfected with the human high affinity IgE receptor (FcεRIH). More recently, humanized RBL cell lines saw the introduction of reporter genes such as luciferase (RS-ATL8) and DsRed (RBL NFAT-DsRed). These reporters are more sensitive than their parental non-reporter humanized RBL cell lines.

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Article Synopsis
  • The study focuses on PfRH5, a key target for new malaria vaccines, and investigates how human antibodies can provide immunity against this protein.
  • Researchers isolated human monoclonal antibodies from vaccine trial participants, identifying both neutralizing mAbs that target distinct sites and non-functional or antagonistic mAbs.
  • A novel subset of non-neutralizing antibodies was found to slow down the invasion of red blood cells by the malaria parasite, enhancing the effectiveness of neutralizing antibodies and informing future vaccine design strategies.
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The most widespread form of malaria is caused by Plasmodium vivax. To replicate, this parasite must invade immature red blood cells through a process requiring interaction of the P. vivax Duffy binding protein (PvDBP) with its human receptor, the Duffy antigen receptor for chemokines.

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Malaria vaccine design and prioritization has been hindered by the lack of a mechanistic correlate of protection. We previously demonstrated a strong association between protection and merozoite-neutralizing antibody responses following vaccination of non-human primates against Plasmodium falciparum reticulocyte binding protein homolog 5 (PfRH5). Here, we test the mechanism of protection.

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Article Synopsis
  • The development of liver-humanized mouse models allows researchers to study the preerythrocytic stages of malaria, a significant advancement compared to the limited existing models for blood stage infection.
  • Current methods involve injecting human red blood cells (hRBCs) to study malaria in small animals, but these treatments do not replicate the natural infection process that occurs via mosquito bites.
  • The newly established FRGN KO mouse model, which incorporates human hepatocytes and allows for both liver and blood stage infection studies, demonstrates promise in testing therapeutic interventions like monoclonal antibodies against specific parasite proteins.
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malaria continues to evade control efforts, utilizing highly specialized sexual-stages to transmit infection between the human host and mosquito vector. In a vaccination model, antibodies directed to sexual-stage antigens, when ingested in the mosquito blood meal, can inhibit parasite growth in the midgut and consequently arrest transmission. Despite multiple datasets for the sexual-stage transcriptome and proteome, there have been no rational screens to identify candidate antigens for transmission-blocking vaccine (TBV) development.

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The Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) has recently emerged as a leading candidate antigen against the blood-stage human malaria parasite. However it has proved challenging to identify a heterologous expression platform that can produce a soluble protein-based vaccine in a manner compliant with current Good Manufacturing Practice (cGMP). Here we report the production of full-length PfRH5 protein using a cGMP-compliant platform called ExpreS(2), based on a Drosophila melanogaster Schneider 2 (S2) stable cell line system.

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Antigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of the human malaria parasite Plasmodium falciparum. To date, only strain-specific protection has been reported by trials of such vaccines in nonhuman primates. We recently showed that P.

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Background: Parasite-specific IgE is thought to correlate with protection against Schistosoma mansoni infection or re-infection. Only a few molecular targets of the IgE response in S. mansoni infection have been characterised.

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There is intense interest in induction and characterization of strain-transcending neutralizing Ab against antigenically variable human pathogens. We have recently identified the human malaria parasite Plasmodium falciparum reticulocyte-binding protein homolog 5 (PfRH5) as a target of broadly neutralizing Abs, but there is little information regarding the functional mechanism(s) of Ab-mediated neutralization. In this study, we report that vaccine-induced polyclonal anti-PfRH5 Abs inhibit the tight attachment of merozoites to erythrocytes and are capable of blocking the interaction of PfRH5 with its receptor basigin.

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